Experiences of employment among young people with juvenile idiopathic arthritis: a qualitative study.

PubMed

Hanson, Helen; Hart, Ruth I; Thompson, Ben; McDonagh, Janet E; Tattersall, Rachel; Jordan, Alison; Foster, Helen E

2018-08-01

This study explored expectations and experiences of employment among young people with juvenile idiopathic arthritis and the role of health professionals in promoting positive employment outcomes. Semistructured interviews (n = 13) and three focus groups (n = 9, n = 4, n = 3) were conducted with young people (16-25 y) and adults (26-31 y) with juvenile idiopathic arthritis and semistructured interviews (n = 9) were conducted with health professionals. Transcripts were analyzed thematically. Young people with juvenile idiopathic arthritis have concerns about employers' attitudes toward employees with long-term health conditions and lack knowledge of antidiscrimination legislation. Young people not in education, employment or training identify arthritis as a key barrier. Challenges associated with arthritis (e.g., pain, psychological distress) may not be visible to employers. Decisions about disclosing arthritis are challenging and cause anxiety. Young people associate good disease management and access to flexible and convenient care with their capacity to succeed in employment. Psychosocial and vocational interventions have benefited some young people but are not routinely available. Low expectations of employers may affect young people's decisions about disclosure and seeking appropriate support in the work place. Health professionals can equip young people with knowledge and skills to negotiate appropriate support, through signposting to antidiscrimination information and offering practice of transferable skills such as disclosure in consultations. Implications for rehabilitation Young people with juvenile idiopathic arthritis encounter challenges with regard to employment; many lack the knowledge and skills to negotiate appropriate support from employers. Rehabilitation professionals could play a more substantial role in equipping them with relevant knowledge and skills by signposting to antidiscrimination information and nurturing

Trial of early aggressive therapy in polyarticular juvenile idiopathic arthritis.

PubMed

Wallace, Carol A; Giannini, Edward H; Spalding, Steven J; Hashkes, Philip J; O'Neil, Kathleen M; Zeft, Andrew S; Szer, Ilona S; Ringold, Sarah; Brunner, Hermine I; Schanberg, Laura E; Sundel, Robert P; Milojevic, Diana; Punaro, Marilynn G; Chira, Peter; Gottlieb, Beth S; Higgins, Gloria C; Ilowite, Norman T; Kimura, Yukiko; Hamilton, Stephanie; Johnson, Anne; Huang, Bin; Lovell, Daniel J

2012-06-01

To determine whether aggressive treatment initiated early in the course of rheumatoid factor (RF)-positive or RF-negative polyarticular juvenile idiopathic arthritis (JIA) can induce clinical inactive disease within 6 months. Between May 2007 and October 2010, a multicenter, prospective, randomized, double-blind, placebo-controlled trial of 2 aggressive treatments was conducted in 85 children ages 2-16 years with polyarticular JIA of <12 months' duration. Patients received either methotrexate (MTX) 0.5 mg/kg/week (maximum 40 mg) subcutaneously, etanercept 0.8 mg/kg/week (maximum 50 mg), and prednisolone 0.5 mg/kg/day (maximum 60 mg) tapered to 0 by 17 weeks (arm 1), or MTX (same dosage as arm 1), etanercept placebo, and prednisolone placebo (arm 2). The primary outcome measure was clinical inactive disease at 6 months. An exploratory phase determined the rate of clinical remission on medication (6 months of continuous clinical inactive disease) at 12 months. By 6 months, clinical inactive disease had been achieved in 17 (40%) of 42 patients in arm 1 and 10 (23%) of 43 patients in arm 2 (χ(2) = 2.91, P = 0.088). After 12 months, clinical remission on medication was achieved in 9 patients in arm 1 and 3 patients in arm 2 (P = 0.053). There were no significant interarm differences in adverse events. Although this study did not meet its primary end point, early aggressive therapy in this cohort of children with recent-onset polyarticular JIA resulted in clinical inactive disease by 6 months and clinical remission on medication within 12 months of treatment in substantial proportions of patients in both arms. Copyright © 2012 by the American College of Rheumatology.

Efficacy of adalimumab in young children with juvenile idiopathic arthritis and chronic uveitis: a case series.

PubMed

La Torre, Francesco; Cattalini, Marco; Teruzzi, Barbara; Meini, Antonella; Moramarco, Fulvio; Iannone, Florenzo

2014-05-24

Juvenile idiopathic arthritis is a relatively common chronic disease of childhood, and is associated with persistent morbidity and extra-articular complications, one of the most common being uveitis. The introduction of biologic therapies, particularly those blocking the inflammatory mediator tumor necrosis factor-α, provided a new treatment option for juvenile idiopathic arthritis patients who were refractory to standard therapy such as non-steroidal anti-inflammatory drugs, corticosteroids and/or methotrexate. The first case was a 2-year-old girl with juvenile idiopathic arthritis and uveitis who failed to respond to treatment with anti-inflammatories, low-dose corticosteroids and methotrexate, and had growth retardation. Adalimumab 24 mg/m2 every 2 weeks and prednisone 0.5 mg/kg/day were added to methotrexate therapy; steroid tapering and withdrawal started after 1 month. After 2 months the patient showed good control of articular and ocular manifestations, and she remained in remission for 1 year, receiving adalimumab and methotrexate with no side effects, and showing significant improvement in growth. Case 2 was a 9-year-old boy with an 8-year history of juvenile idiopathic arthritis and uveitis that initially responded to infliximab, but relapse occurred after 2 years off therapy. After switching to adalimumab, and adjusting doses of both adalimumab and methotrexate based on body surface area, the patient showed good response and corticosteroids were tapered and withdrawn after 6 months; the patient remained in remission taking adalimumab and methotrexate. The final case was a 5-year-old girl with juvenile idiopathic arthritis for whom adalimumab was added to methotrexate therapy after three flares of uveitis. The patient had two subsequent episodes of uveitis that responded well to local therapy, but was then free of both juvenile idiopathic arthritis and uveitis symptoms, allowing methotrexate and then adalimumab to be stopped; the patient remained in drug

Efficacy of adalimumab in young children with juvenile idiopathic arthritis and chronic uveitis: a case series

PubMed Central

2014-01-01

Background Juvenile idiopathic arthritis is a relatively common chronic disease of childhood, and is associated with persistent morbidity and extra-articular complications, one of the most common being uveitis. The introduction of biologic therapies, particularly those blocking the inflammatory mediator tumor necrosis factor-α, provided a new treatment option for juvenile idiopathic arthritis patients who were refractory to standard therapy such as non-steroidal anti-inflammatory drugs, corticosteroids and/or methotrexate. Case presentations The first case was a 2-year-old girl with juvenile idiopathic arthritis and uveitis who failed to respond to treatment with anti-inflammatories, low-dose corticosteroids and methotrexate, and had growth retardation. Adalimumab 24 mg/m2 every 2 weeks and prednisone 0.5 mg/kg/day were added to methotrexate therapy; steroid tapering and withdrawal started after 1 month. After 2 months the patient showed good control of articular and ocular manifestations, and she remained in remission for 1 year, receiving adalimumab and methotrexate with no side effects, and showing significant improvement in growth. Case 2 was a 9-year-old boy with an 8-year history of juvenile idiopathic arthritis and uveitis that initially responded to infliximab, but relapse occurred after 2 years off therapy. After switching to adalimumab, and adjusting doses of both adalimumab and methotrexate based on body surface area, the patient showed good response and corticosteroids were tapered and withdrawn after 6 months; the patient remained in remission taking adalimumab and methotrexate. The final case was a 5-year-old girl with juvenile idiopathic arthritis for whom adalimumab was added to methotrexate therapy after three flares of uveitis. The patient had two subsequent episodes of uveitis that responded well to local therapy, but was then free of both juvenile idiopathic arthritis and uveitis symptoms, allowing methotrexate and then adalimumab to be

Treatment of juvenile idiopathic arthritis-associated uveitis: challenges and update.

PubMed

Rabinovich, C Egla

2011-09-01

To update the current understanding of the risk factors for poor outcomes in juvenile idiopathic arthritis-related uveitis. In addition, current therapies, both traditional and biological, are reviewed. Male sex, independent of age or antinuclear antibody status, is associated with increased ocular morbidity. Having anterior chamber inflammation on first exam increases the risk of developing vision-threatening eye complications. Presence of one complication increases the risk of developing another. Risk of cataract development associated with topical glucocorticoid use is better defined. Longer duration of remission on therapy has been found to decrease the risk of disease flare after discontinuation of methotrexate. Recent studies of both nonbiological and biological therapies for arthritis-related uveitis are discussed. With a better understanding of risk factors associated with the ocular morbidity of uveitis associated with juvenile idiopathic arthritis, aggressive therapies can be targeted for improved visual outcomes. Alternative treatments to avoid long-term corticosteroid use include the use of antimetabolites and biological therapies. More prospective comparator studies and/or use of multicenter databases are needed to better understand best treatments.

Prevalence and incidence of juvenile idiopathic arthritis: a systematic review.

PubMed

Thierry, Sigrid; Fautrel, Bruno; Lemelle, Irène; Guillemin, Francis

2014-03-01

To conduct a systematic literature review on incidence and prevalence of juvenile idiopathic arthritis and to estimate these figures in Europe for 2010. Articles on incidence or prevalence of juvenile idiopathic arthritis were searched in Medline. Pooled incidence and prevalence were calculated overall, by gender, age, classification and arthritis categories. We used the available age and gender pooled rates to standardize the incidence and prevalence on the 2010 European population and estimate the number of cases in Europe in 2010. Forty-three articles (33 on incidence, 29 on prevalence) were included. Incidence rates varied from 1.6 to 23 and prevalence from 3.8 to 400/100,000. Pooled incidence and prevalence were higher for girls (10.0 [9.4-10.7] and 19.4 [18.3-20.6]/100,000) than boys (5.7 [5.3-6.2] and 11.0 [10.2-11.9]/100,000). Oligoarthritis was the most frequent form (pooled incidence rate 3.7 [3.5-3.9] and prevalence 16.8 [15.9-17.7]/100,000). The direct standardized incidence rate was 8.2 [7.5-9.0] and prevalence 70.2 [62.9-78.1]/100,000. In Europe in 2010, the estimated number of incident cases was 6896 [5481-8578] and 59,175 [44,256-76,983] prevalent cases. Incidence and prevalence varied greatly among published reports of juvenile idiopathic arthritis, which may be explained by methodological issues, classification used, and time. Estimating the number of affected children can be useful, especially with the new treatment possibilities. Copyright © 2013 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Facial morphology in children and adolescents with juvenile idiopathic arthritis and moderate to severe temporomandibular joint involvement.

PubMed

Hsieh, Yuh-Jia; Darvann, Tron A; Hermann, Nuno V; Larsen, Per; Liao, Yu-Fang; Bjoern-Joergensen, Jens; Kreiborg, Sven

2016-02-01

The aims of this study were to (1) assess lateral facial morphology in children and adolescents with juvenile idiopathic arthritis and moderate to severe temporomandibular joint (TMJ) involvement, (2) compare the lateral facial morphology of these subjects with and without TMJ involvement using cephalograms and 3-dimensional (3D) facial photographs, and (3) compare and correlate the results of the 3D photographic and cephalometric analyses. Sixty patients with juvenile idiopathic arthritis were included and grouped as follows: group 1, juvenile idiopathic arthritis patients without TMJ involvement; group 2, juvenile idiopathic arthritis patients with moderate to severe unilateral TMJ involvement; and group 3, juvenile idiopathic arthritis patients with moderate to severe bilateral TMJ involvement. Lateral cephalograms were used to assess and compare lateral facial morphologies between the groups. Lateral projections of oriented 3D photographs were superimposed on the lateral cephalograms. The results of the lateral 3D photographic analysis were correlated with those of lateral cephalometric analysis. Group 3 showed the most severe growth disturbances, including more retrognathic mandible and retruded chin, steep occlusal and mandibular planes, and more hyperdivergent type (P <0.01). Group 2 showed similar growth disturbances, but to a lesser extent than did group 3. Photographic variables were significantly correlated with the soft tissue and skeletal variables of cephalograms (0.5 < r < 0.9; P <0.001). Subjects with juvenile idiopathic arthritis and unilateral or bilateral moderate to severe TMJ involvement had significant growth disturbances. Early intervention is recommended for these patients to prevent unfavorable facial development. Furthermore, with proper orientation, 3D photographs can be used as an alternative to conventional lateral cephalograms and 2-dimensional photographs. Copyright © 2016 American Association of Orthodontists. Published by Elsevier

Physiotherapy in pauciarticular juvenile idiopathic arthritis. Case study.

PubMed

Zuk, Beata; Kaczor, Zofia; Zuk-Drążyk, Berenika; Księżopolska-Orłowska, Krystyna

2014-01-01

Juvenile idiopathic arthritis (JIA) is the most common arthropathy of childhood and adolescence. This term encompasses a group of chronic systemic inflammatory diseases of the connective tissue which cause arthritis in patients under 16 years of age lasting at least 6 weeks. The authors presented the characteristic features of physiotherapy based on functional examination results on the basis of two cases of girls with pauciarticular JIA treated according to an established pharmacological regimen. Physiotherapy should be introduced at an early stage of the disease. Kinesiotherapy preceded by history-taking and a functional examination of the patient, has to focus on both primary and secondary joint lesions.

Judicious use of biologicals in juvenile idiopathic arthritis.

PubMed

Zhao, Yongdong; Wallace, Carol

2014-11-01

Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disorder that may cause joint destruction. Biological treatments targeting specific cytokines and cell interactions have transformed the outcomes of JIA. This review focuses on the selection of patients for and the timing and selection of biological treatment in JIA. Tumor necrosis factor (TNF) inhibitors remain the first choice for polyarticular JIA, followed by abatacept and tocilizumab. Monoclonal-antibody TNF inhibitors and abatacept are usually chosen for methotrexate-resistant uveitis. Recent clinical trials of canakinumab, rilonacept, and tocilizumab have obtained great improvement in both systemic and arthritic features in chronic systemic JIA patients. Current guidelines support the early use of a short-acting IL-1 antagonist for macrophage activation syndrome, a life-threatening complication. TREAT and ACUTE studies suggest that a therapeutic window of opportunity during early disease may exist in JIA. Early initiation of biological therapy may be associated with slower progression of joint damage and longer remission.

Ultrasound-guided corticosteroid injection of the subtalar joint for treatment of juvenile idiopathic arthritis.

PubMed

Young, Cody M; Horst, Deanna M; Murakami, James W; Shiels, William E

2015-07-01

The subtalar joint is commonly affected in children with juvenile idiopathic arthritis and is challenging to treat percutaneously. To describe the technique for treating the subtalar joint with US-guided corticosteroid injections in children and young adults with juvenile idiopathic arthritis and to evaluate the safety of the treatment. We retrospectively analyzed 122 patients (age 15 months-29 years) with juvenile idiopathic arthritis who were referred by a pediatric rheumatologist for corticosteroid injection therapy for symptoms related to the hindfoot or ankle. In these patients the diseased subtalar joint was targeted for therapy, often in conjunction with adjacent affected joints or tendon sheaths of the ankle. We used a protocol based on age, weight and joint for triamcinolone hexacetonide or triamcinolone acetonide dose prescription. We describe the technique for successful treatment of the subtalar joint. A total of 241 subtalar joint corticosteroid injections were performed under US guidance, including 68 repeat injections for recurrent symptoms in 26 of the 122 children and young adults. The average time interval between repeat injections was 24.8 months (range 2.2-130.7 months, median 14.2 months). Subcutaneous tissue atrophy and skin hypopigmentation were the primary complications observed. These complications occurred in 3.9% of the injections. With appropriate training and practice, the subtalar joint can be reliably and safely targeted with US-guided corticosteroid injection to treat symptoms related to juvenile idiopathic arthritis.

[Interdisciplinary and evidence-based treatment guideline for juvenile idiopathic arthritis].

PubMed

Guellac, N; Niehues, T

2008-01-01

Treatment of Juvenile Idiopathic Arthritis (JIA) has improved quality of life in children and adolescents suffering from JIA. However, it varies considerably from caregiver to caregiver. Therefore a standardisation of care on the basis of consensus treatment recommendations offers the chance to further improve the quality of care for children and adolescents with JIA. We aimed to establish an interdisciplinary, evidence-based treatment guideline for JIA based on the existing guideline from 2005. We did a systematic literature analysis in PUBMED with the key words "juvenile idiopathic (rheumatoid) arthritis" and "therapy". As limits in PUBMED we used: humans, published in the last 3 years, all child 0-18 years, clinical trial. Studies relating to diagnosis of JIA, Uveitis, vaccination, transition and rofexocibe were excluded. Authors of the 2005 guideline and representatives nominated by different societies were invited to attend the consensus conferences which were hosted by a professional moderator. Following societies were invited: Berufsverband der Kinder- und Jugendärzte (BVKJ), Deutsche Gesellschaft für Kinder- und Jugendmedizin (DGKJ), Deutsche Gesellschaft für Rheumatologie (DGRh), Deutsche Ophthalmologische Gesellschaft (DOG), Deutsche Rheuma-Liga Bundesverband, Verein zur Förderung und Unterstützung rheumatologisch erkrankter Kinder und deren Eltern, Vereinigung für Kinderorthopädie, Zentraler Verband der Physiotherapeuten und Krankengymnasten (ZVK). Consensus conferences took place in Düsseldorf on May 9th and August 1st 2007 and were each attended by more than 95% of the nominated representatives Finally, statements were confirmed in a Delphi method. Consensus statements regarding drug therapy, symptomatic and surgical management of JIA were compiled and judged strictly by the criteria of Evidence-Based Medicine (EBM).

Ultrasound-guided corticosteroid injection therapy for juvenile idiopathic arthritis: 12-year care experience.

PubMed

Young, Cody M; Shiels, William E; Coley, Brian D; Hogan, Mark J; Murakami, James W; Jones, Karla; Higgins, Gloria C; Rennebohm, Robert M

2012-12-01

Intra-articular corticosteroid injections are a safe and effective treatment for patients with juvenile idiopathic arthritis. The potential scope of care in ultrasound-guided corticosteroid therapy in children and a joint-based corticosteroid dose protocol designed to optimize interdisciplinary care are not found in the current literature. The purpose of this study was to report the spectrum of care, technique and safety of ultrasound-guided corticosteroid injection therapy in patients with juvenile idiopathic arthritis and to propose an age-weight-joint-based corticosteroid dose protocol. A retrospective analysis was performed of 198 patients (ages 21 months to 28 years) referred for treatment of juvenile idiopathic arthritis with corticosteroid therapy. Symptomatic joints and tendon sheaths were treated as prescribed by the referring rheumatologist. An age-weight-joint-based dose protocol was developed and utilized for corticosteroid dose prescription. A total of 1,444 corticosteroid injections (1,340 joints, 104 tendon sheaths) were performed under US guidance. Injection sites included small, medium and large appendicular skeletal joints (upper extremity 497, lower extremity 837) and six temporomandibular joints. For patients with recurrent symptoms, 414 repeat injections were performed, with an average time interval of 17.7 months (range, 0.5-101.5 months) between injections. Complications occurred in 2.6% of injections and included subcutaneous tissue atrophy, skin hypopigmentation, erythema and pruritis. US-guided corticosteroid injection therapy provides dynamic, precise and safe treatment of a broad spectrum of joints and tendon sheaths throughout the entire pediatric musculoskeletal system. An age-weight-joint-based corticosteroid dose protocol is effective and integral to interdisciplinary care of patients with juvenile idiopathic arthritis.

Anti-adalimumab antibodies in juvenile idiopathic arthritis-related uveitis.

PubMed

Leinonen, Sanna T; Aalto, Kristiina; Kotaniemi, Kaisu M; Kivelä, Tero T

2017-01-01

To evaluate the association of adalimumab trough levels and anti-adalimumab antibodies with activity of uveitis in juvenile idiopathic arthritis-related uveitis. This was a retrospective observational case series in a clinical setting at the Department of Ophthalmology, Helsinki University Hospital, Finland in 2014-2016. Thirty-one paediatric patients with chronic anterior juvenile idiopathic arthritis-related uveitis in 58 eyes and who had been on adalimumab ≥6 months were eligible for the study. Uveitis activity during adalimumab treatment, adalimumab trough levels and anti-adalimumab antibody levels were recorded. Anti-adalimumab antibody levels ≥12 AU /ml were detected in nine patients (29%). This level of anti-adalimumab antibodies was associated with a higher grade of uveitis (p<0.001), uveitis that was not in remission (p=0.001) and with lack of concomitant methotrexate therapy (p=0.043). In patients with anti-adalimumab antibody levels <12 AU/ml, higher serum trough levels did not associate with better control of uveitis (p=0.86). Adalimumab treatment might be better guided by monitoring anti-adalimumab antibody formation in treating JIA-related uveitis.

Australian Paediatric Rheumatology Group standards of care for the management of juvenile idiopathic arthritis.

PubMed

Munro, Jane; Murray, Kevin; Boros, Christina; Chaitow, Jeffrey; Allen, Roger C; Akikusa, Jonathan; Adib, Navid; Piper, Susan E; Singh-Grewal, Davinder

2014-09-01

This standards document outlines accepted standards of management for children, adolescents and young adults with juvenile idiopathic arthritis (JIA) in Australia. This document acknowledges that the chronic inflammatory arthritis conditions (JIA) in childhood are different diseases from inflammatory arthritis in adults and that specific expertise is required in the care of children with arthritis. © 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Updates on the risk markers and outcomes of severe juvenile idiopathic arthritis-associated uveitis

PubMed Central

Angeles-Han, Sheila T; Yeh, Steven; Vogler, Larry B

2013-01-01

Uveitis is the most common extra-articular manifestation of juvenile idiopathic arthritis, which is the most common systemic cause of uveitis in children. Known risk factors for uveitis include antinuclear antibody seropositivity, young age of arthritis onset, specific juvenile idiopathic arthritis subtype and short duration of disease. Risk markers for severe ocular disease include gender, age and complications at initial visit. Due to the risk for vision-compromising sequelae such as cataracts, band keratopathy, glaucoma, vision loss and blindness, an understanding of the risk factors for uveitis development and severe ocular disease is crucial to help prevent serious visual disability and complications. This paper reviews the pathogenesis of uveitis, known risk factors for uveitis development and severe visual outcome, and addresses the need for additional biomarkers of uveitis risk, prognosis and remission. PMID:24187594

Juvenile idiopathic arthritis profile in Turkish children.

PubMed

Yilmaz, Mustafa; Kendirli, Seval G; Altintas, Derya U; Karakoc, Gulbin B; Inal, Ayfer; Kilic, Mehmet

2008-04-01

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of disorders. Publications from different countries point to differences in the disease manifestation of JIA among different populations. The aim of the present paper was to evaluate the clinical and laboratory features of JIA in Turkish children. A total of 196 JIA patients who fulfilled International League of Associations for Rheumatology (ILAR) diagnostic criteria were included in this retrospective study. The data collected were age, gender, age at disease onset and at diagnosis, and follow-up duration. Antinuclear antibody (ANA), rheumatoid factor (RF), and human leukocyte antigen B-27 were evaluated for each patient. There were 102 boys and 94 girls with a mean duration of disease of 4.1 years. The mean age at the first visit was 8.8 years, and the mean age at onset of disease was 6.8 years (range, 8 months-15 years). Polyarticular JIA was the most frequent onset type (37.2%). Other subtypes included oligoarthritis (34.2%), systemic arthritis (15.3%), psoriatic arthritis (1%), enthesitis-related arthritis (9.7%), and other arthritis (2.2%). ANA was positive in 28 patients (14.2%). Chronic uveitis occurred in two patients with oligoarthritis; and two patients with enthesitis-related arthritis had acute uveitis. Three patients (1.4%) developed amyloidosis. Compared to reports from Western countries, remarkably different features of JIA were found in Turkish children, which included higher frequency of polyarticular JIA, higher prevalence among boys, lower rate of ANA positivity and uveitis. Further studies are required to understand how genetic and environmental differences affect JIA expression.

Evaluation of Fitness and the Balance Levels of Children with a Diagnosis of Juvenile Idiopathic Arthritis: A Pilot Study

PubMed Central

Maggio, Maria Cristina; Corsello, Giovanni; Messina, Giuseppe; Iovane, Angelo; Palma, Antonio

2017-01-01

Background: Juvenile idiopathic arthritis is a main cause of physical disability and has high economic costs for society. The purpose of this study was to assess the fitness levels and the postural and balance deficits with a specific test battery. Methods: Fifty-six subjects were enrolled in this study. Thirty-nine healthy subjects were included in the control group and seventeen in the juvenile idiopathic arthritis group. All subjects were evaluated using a posturography system. The fitness level was evaluated with a battery of tests (Abalakov test, sit-up test, hand grip test, backsaver sit and reach, the toe touch test). An unpaired t-test was used to determine differences. Pearson’s correlation coefficient was used to evaluate the correlation between the tests. Results: The battery of tests demonstrated that subjects in the juvenile idiopathic arthritis group have lower fitness levels compared to the control group. The juvenile idiopathic arthritis group showed low postural control with respect to the control group. Pearson analysis of the juvenile idiopathic arthritis group data showed significant correlations between variables. Pearson’s results from the control group data showed a similar trend. Conclusions: The results suggest that the battery of tests used could be an appropriate tool. However, we highlight that these conclusions need to be supported by other studies with a larger population scale. PMID:28753965

Evaluation of Fitness and the Balance Levels of Children with a Diagnosis of Juvenile Idiopathic Arthritis: A Pilot Study.

PubMed

Patti, Antonino; Maggio, Maria Cristina; Corsello, Giovanni; Messina, Giuseppe; Iovane, Angelo; Palma, Antonio

2017-07-19

Background: Juvenile idiopathic arthritis is a main cause of physical disability and has high economic costs for society. The purpose of this study was to assess the fitness levels and the postural and balance deficits with a specific test battery. Methods: Fifty-six subjects were enrolled in this study. Thirty-nine healthy subjects were included in the control group and seventeen in the juvenile idiopathic arthritis group. All subjects were evaluated using a posturography system. The fitness level was evaluated with a battery of tests (Abalakov test, sit-up test, hand grip test, backsaver sit and reach, the toe touch test). An unpaired t -test was used to determine differences. Pearson's correlation coefficient was used to evaluate the correlation between the tests. Results: The battery of tests demonstrated that subjects in the juvenile idiopathic arthritis group have lower fitness levels compared to the control group. The juvenile idiopathic arthritis group showed low postural control with respect to the control group. Pearson analysis of the juvenile idiopathic arthritis group data showed significant correlations between variables. Pearson's results from the control group data showed a similar trend. Conclusions: The results suggest that the battery of tests used could be an appropriate tool. However, we highlight that these conclusions need to be supported by other studies with a larger population scale.

Uveitis associated with juvenile idiopathic arthritis.

PubMed

Sen, Ethan S; Dick, Andrew D; Ramanan, Athimalaipet V

2015-06-01

Uveitis is a potentially sight-threatening complication of juvenile idiopathic arthritis (JIA). JIA-associated uveitis is recognized to have an autoimmune aetiology characterized by activation of CD4(+) T cells, but the underlying mechanisms might overlap with those of autoinflammatory conditions involving activation of innate immunity. As no animal model recapitulates all the features of JIA-associated uveitis, questions remain regarding its pathogenesis. The most common form of JIA-associated uveitis is chronic anterior uveitis, which is usually asymptomatic initially. Effective screening is, therefore, essential to detect early disease and commence treatment before the development of visually disabling complications, such as cataracts, glaucoma, band keratopathy and cystoid macular oedema. Complications can result from uncontrolled intraocular inflammation as well as from its treatment, particularly prolonged use of high-dose topical corticosteroids. Accumulating evidence supports the early introduction of systemic immunosuppressive drugs, such as methotrexate, as steroid-sparing agents. Prospective randomized controlled trials of TNF inhibitors and other biologic therapies are underway or planned. Future research should aim to identify biomarkers to predict which children are at high risk of developing JIA-associated uveitis or have a poor prognosis. Such biomarkers could help to ensure that patients receive earlier interventions and more-potent therapy, with the ultimate aim of reducing loss of vision and ocular morbidity.

Anticyclic citrullinated peptide antibodies in juvenile idiopathic arthritis.

PubMed

Brunner, Jürgen K H; Sitzmann, Friedrich C

2006-01-01

Anticyclic citrullinated peptide (anti-CCP) antibodies have been detected in patients with juvenile idiopathic arthritis (JRA), particularly in those with polyarticular JIA. We analyzed the presence of anti-CCP antibodies of the IgG class in sera of patients with defined juvenile idiopathic arthritis (JIA) of various subgroups. One hundred and fifty-nine serum samples were investigated. Forty-five patients were diagnosed with JIA (15 male and 30 female) aged 1.9-17.3 years (median 12.9, mean 11.0). Thirty-eight samples were taken from patients suffering from other autoimmunopathies and 34 patients with other underlying diseases were taken at different time points in their disease course. Under 42 samples were taken from patients with noninflammatory diseases. Enzyme-linked immunosorbent assay (ELISA) was used for the detection of anti-CCP antibodies. Anti-CCP antibodies were found in 6.9% of all samples and in 4.4% patients with JIA. Disease duration and medication did not differ significantly between anti-CCP positive and negative patients. A review of the literature and our own results shows that anti-CCP antibodies can be detected in the sera of only some patients with JIA. Routine determination of anti-CCP cannot be recommended.

Update on the medical treatment of juvenile idiopathic arthritis.

PubMed

Hashkes, Philip J; Laxer, Ronald M

2006-12-01

Many exciting developments in the treatment of juvenile idiopathic arthritis (JIA) have emerged recently, including new tools to assess the results of clinical trials (eg, the definition of remission and a radiologic scoring tool). New controlled studies examined the equivalence of meloxicam to naproxen, the efficacy of leflunomide but the superiority of methotrexate, and the use of infliximab in polyarthritis JIA. Initial studies have shown the potential of anti-interleukin (IL)-1 and anti-IL-6 receptor antibody therapy for systemic JIA. Corticosteroid-sparing medications including the use of "biologic modifiers" for JIA-associated uveitis have been described. Evidence-based guidelines for the main subtypes of JIA have been published. However, good evidence on the treatment of several disease subtypes is still lacking. Studies of new medications and the use of combination therapy, including aggressive induction therapy early in the disease course, are necessary to continue improving the outcome of JIA patients.

Specialty Practice and Cost Considerations in the Management of Uveitis Associated With Juvenile Idiopathic Arthritis.

PubMed

Palestine, Alan G; Singh, Jasleen K; Kolfenbach, Jason R; Ozzello, Daniel J

2016-07-01

To evaluate whether cost, prior insurance authorization concerns, and subspecialty practice influence therapeutic decisions in the treatment of uveitis associated with juvenile idiopathic arthritis. A total of 2,965 pediatric ophthalmologists, uveitis specialists, retina specialists, and rheumatologists across the United States were surveyed via e-mail regarding their choice in long-term therapy for a hypothetical patient with uveitis associated with juvenile idiopathic arthritis. Outcomes of interest were differences in therapy choice based on cost/prior authorization and specialty practice. There were significant differences in the use of methotrexate and biologics among specialists, both with and without consideration for cost and prior authorization. Physicians in four different specialties who treat uveitis associated with juvenile idiopathic arthritis agree on methotrexate as a first-line treatment choice and a biologic immunosuppressive medication as a second choice, but there are significant differences between the specialties in their use of these medications. Cost and insurance considerations did not affect therapy selection. [J Pediatr Ophthalmol Strabismus. 2016;53(4):246-251.]. Copyright 2016, SLACK Incorporated.

[Importance of the new biologicals and cytokine antagonists in the treatment of juvenile idiopathic arthritis (JIA)].

PubMed

Horneff, G

2005-06-01

Juvenile idiopathic arthritis is group of diseases of unknown aetiology characterised by the occurrence of chronic arthritis during childhood. Compared to adult onset rheumatoid arthritis, its course is more variable. Increasing knowledge of the inflammatory process as well as in molecular genetics and biotechnology has enable the production of new drugs, the biologicals. These are able to specifically block mechanisms of immune activation and thereby interfere with the inflammatory process. An increasing number of biologicals have been tried in clinical studies in adults suffering from rheumatoid arthritis, psoriasis or psoriasis arthritis and a couple of them were already licensed for treatment. Treatment of juvenile idiopathic arthritis by blockade of tumournecrosis-factor (TNF) using the soluble receptor Etanercept or the monoclonal antibodies Infliximab and Adalimumab showed comparable clinical efficacy. Blockade of TNF therefore already reached a certain place in the therapeutic algorythm for treatment of juvenile idiopathic arthritis. Currently, only Etanercept is licensed for treatment of active juvenile polyarthritis refractory to methotrexate. Studies using Infliximab and Adalimumab will be completed in the near future. However, antibodies blocking TNF may already be used in patients suffering from active uncontrolled chronic uveitis in whom visual impairment is threatening. TNF blockers may also be indicated in juvenile ankylosing spondylitis. The use of further biologicals, the interleukin-1 receptor antagonist Anakinra, Atlizumab (MRA) blocking the receptor for interleukin-6 or Abatacept, an inhibitory ligand of the co-stimulatory T cell membrane molecule CD28, remain experimental and should be preserved for clinical studies.

Rheumatoid Arthritis-Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis: Shared Mechanistic and Phenotypic Traits Suggest Overlapping Disease Mechanisms.

PubMed

Paulin, Francisco; Doyle, Tracy J; Fletcher, Elaine A; Ascherman, Dana P; Rosas, Ivan O

2015-01-01

The prevalence of clinically evident interstitial lung disease in patients with rheumatoid arthritis is approximately 10%. An additional 33% of undiagnosed patients have interstitial lung abnormalities that can be detected with high-resolution computed tomography. Rheumatoid arthritis-interstitial lung disease patients have three times the risk of death compared to those with rheumatoid arthritis occurring in the absence of interstitial lung disease, and the mortality related to interstitial lung disease is rising. Rheumatoid arthritis-interstitial lung disease is most commonly classified as the usual interstitial pneumonia pattern, overlapping mechanistically and phenotypically with idiopathic pulmonary fibrosis, but can occur in a non-usual interstitial pneumonia pattern, mainly nonspecific interstitial pneumonia. Based on this, we propose two possible pathways to explain the coexistence of rheumatoid arthritis and interstitial lung disease: (i) Rheumatoid arthritis-interstitial lung disease with a non-usual interstitial pneumonia pattern may come about when an immune response against citrullinated peptides taking place in another site (e.g. the joints) subsequently affects the lungs; (ii) Rheumatoid arthritis-interstitial lung disease with a usual interstitial pneumonia pattern may represent a disease process in which idiopathic pulmonary fibrosis-like pathology triggers an immune response against citrullinated proteins that promotes articular disease indicative of rheumatoid arthritis. More studies focused on elucidating the basic mechanisms leading to different sub-phenotypes of rheumatoid arthritis-interstitial lung disease and the overlap with idiopathic pulmonary fibrosis are necessary to improve our understanding of the disease process and to define new therapeutic targets.

Chronic Non-infectious Uveitis in Patients with Juvenile Idiopathic Arthritis.

PubMed

Kolomeyer, Anton M; Tu, Yufei; Miserocchi, Elisabetta; Ranjan, Mangala; Davidow, Amy; Chu, David S

2016-08-01

To describe clinical findings and analyze treatment evolution of chronic, non-infectious uveitis in patients with juvenile idiopathic arthritis (JIA). A total of 82 patients (147 eyes) with JIA-related uveitis treated for ≥2 months were included (78% females; 79% bilateral uveitis; 74% anterior uveitis). Outcome measures were visual acuity (VA), inflammation control, side-effects, and surgical procedures. Mean ± SD age at diagnosis was 4.9 ± 3.8 years; mean ± SD follow-up time was 8.7 ± 7.8 years. Mean VA did not significantly change throughout the study. Three (2%) eyes resulted in no light perception (NLP) vision. Thirty (37%) patients underwent 69 procedures. In total, 41 (50%) patients achieved inflammation control. TNF-α inhibitors were significantly associated with inflammation control. Seven (8.5%) patients stopped treatment due to side-effects. JIA is a cause of significant ocular morbidity. TNF-α inhibitor use was associated with inflammation control. Prospective, randomized, double blind clinical trials in this regard are warranted.

[Juvenile idiopathic arthritis and oral health].

PubMed

Kobus, Agnieszka; Kierklo, Anna; Sielicka, Danuta; Szajda, Sławomir Dariusz

2016-05-04

Juvenile idiopathic arthritis (JIA) is the most common autoimmune inflammatory disease of connective tissue in children. It is characterized by progressive joint destruction which causes preserved changes in the musculoskeletal system. The literature describes fully clinical symptoms and radiological images in different subtypes of JIA. However, there is still a limited number of studies reporting on the medical condition of the oral cavity of ill children. JIA can affect hard and soft tissues of the oral cavity by: the general condition of the child's health, arthritis of the upper limbs, as the result of the pharmacotherapy, changes in secretion and composition of saliva, inflammation of the temporomandibular joint and facial deformity. The study summarizes the available literature on the condition of the teeth and periodontal and oral hygiene in the course of JIA. The presence of diverse factors that modify the oral cavity, such as facial growth, functioning of salivary glands, or the supervision and care provided by adults, prevents clear identification if JIA leads to severe dental caries and periodontal disease. Despite conflicting results in studies concerning the clinical oral status, individuals with JIA require special attention regarding disease prevention and maintenance of oral health.

Identification of dendritic cells in the blood and synovial fluid of children with Juvenile Idiopathic Arthritis.

PubMed

Tabarkiewicz, Jacek; Postępski, Jacek; Olesińska, Edyta; Roliński, Jacek; Tuszkiewicz-Misztal, Ewa

2011-01-01

Childhood chronic arthritis of unknown etiology is known collectively as juvenile idiopathic arthritis (JIA) and consists of heterogeneous subtypes with unique clinical patterns of disease. JIA is the commonest rheumatic disease in children and may still result in significant disability, with joint deformity, growth impairment, and persistence of active arthritis into adulthood. Basic research is rather focused on rheumatoid arthritis, and this lead to small number of publications considering JIA. In this study we examine, by flow cytometry, the expression of dendritic cells (DCs) in the peripheral blood and synovial fluid of children with active JIA in a group of 220 patients. We reveal a significant decrease in the percentage of immature DCs in the blood of patients compared to control children. Surprisingly, we found higher percentages of mature circulating dendritic cells. Both populations of DCs, immature and mature, were accumulated in patients' synovial fluid. We also confirmed the presence of CD206+/CD209+ in JIA samples, which can represent a population of macrophages with dendritic cells morphology. Our results support the thesis that dendritic cells are crucial in the induction and maintenance of autoimmune response and local inflammation during juvenile idiopathic arthritis.

Update on the Treatment of Uveitis in Patients with Juvenile Idiopathic Arthritis: A Review.

PubMed

Asproudis, Ioannis; Katsanos, Andreas; Kozeis, Nikolaos; Tantou, Alexandra; Konstas, Anastasios G

2017-12-01

Chronic uveitis is a common extra-articular manifestation of juvenile idiopathic arthritis. The classic clinical picture is one of chronic anterior uveitis, which usually remains asymptomatic until ocular complications arise. The risk of uveitis is increased in girls with an early onset of oligoarthritis and positive antinuclear antibodies. Even though the inflammation in patients with juvenile idiopathic arthritis is initially limited in the anterior part of the eye, chronic active inflammation may eventually cause significant damage to the posterior pole. Complications may include band keratopathy, cataract, secondary glaucoma, posterior synechiae, cystoid macular edema, and hypotony. The cooperation of ophthalmologists with rheumatologists may help define the best treatment plan. The ophthalmic therapeutic regimen includes topical corticosteroids and mydriatics, while in severe cases immunosuppressive and biological agents are introduced. Surgical management of complications might be needed.

Childhood Arthritis and Rheumatology Research Alliance consensus treatment plans for juvenile idiopathic arthritis-associated and idiopathic chronic anterior uveitis.

PubMed

Angeles-Han, Sheila T; Lo, Mindy S; Henderson, Lauren A; Lerman, Melissa A; Abramson, Leslie; Cooper, Ashley M; Parsa, Miriam F; Zemel, Lawrence S; Ronis, Tova; Beukelman, Timothy; Cox, Erika; Sen, H Nida; Holland, Gary N; Brunner, Hermine I; Lasky, Andrew; Rabinovich, C Egla

2018-05-28

Systemic immunosuppressive treatment of pediatric chronic anterior uveitis (CAU), both juvenile idiopathic arthritis (JIA)-associated and idiopathic varies, making it difficult to identify best treatments. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans (CTPs) for CAU for the purpose of reducing practice variability and allowing future comparison of treatments by comparative effectiveness analysis techniques. A core group of pediatric rheumatologists, ophthalmologists with uveitis expertise, and a lay advisor comprised the CARRA uveitis workgroup who performed literature review on pharmacologic treatments, held teleconferences, and developed a case-based survey administered to the CARRA membership to delineate treatment practices. We utilized 3 face-to-face consensus meetings using nominal group technique to develop CTPs. The survey identified areas of treatment practice variability. We developed 2 CTPs for the treatment of CAU, case definitions, and monitoring parameters. The first CTP is directed at children naïve to steroid-sparing medication, and the second at children initiating biologic therapy with options for methotrexate, adalimumab and infliximab. We defined a core dataset and outcome measures with data collection at 3 and 6 months after therapy initiation. The CARRA membership voted acceptance of the CTPs with a >95% (N = 233) approval. Using consensus methodology, two standardized CTPs were developed for systemic immunosuppressive treatment of CAU. These CTPs are not meant as treatment guidelines, but are designed for further pragmatic research within the CARRA research network. Use of these CTPs in a prospective comparison effectiveness study should improve outcomes by identifying best practice options. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

[The temporomandibular joint in juvenile idiopathic arthritis: what radiologists need to look for on magnetic resonance imaging].

PubMed

De La Hoz Polo, M; Navallas, M

2014-01-01

The term "juvenile idiopathic arthritis" (JIA) encompasses a group of arthritis of unknown cause with onset before the age of 16 years that last for at least 6 weeks. The prevalence of temporomandibular joint involvement in published series ranges from 17% to 87%. Temporomandibular joint involvement is difficult to detect clinically, so imaging plays a key role in diagnosis and monitoring treatment. MRI is the technique of choice for the study of arthritis of the temporomandibular joint because it is the most sensitive technique for detecting acute synovitis and bone edema. Power Doppler ultrasonography can also detect active synovitis by showing the hypervascularization of the inflamed synovial membrane, but it cannot identify bone edema. This article describes the MRI technique for evaluating the temporomandibular joint in patients with juvenile idiopathic arthritis, defines the parameters to look for, and illustrates the main findings. Copyright © 2013 SERAM. Published by Elsevier Espana. All rights reserved.

Patient characteristics associated with response to NSAID monotherapy in children with systemic juvenile idiopathic arthritis.

PubMed

Sura, Anjali; Failing, Christopher; Sturza, Julie; Stannard, Jasmine; Riebschleger, Meredith

2018-01-05

Systemic juvenile idiopathic arthritis (sJIA) is an auto-inflammatory disease characterized by fever, arthritis, and ≥1 of rash, generalized lymphadenopathy, hepato/splenomegaly, and serositis. Non-steroidal anti-inflammatory drugs (NSAIDs) are among the initial treatments of sJIA, but there is currently no evidence indicating which children should undergo a trial of NSAID monotherapy and which should not. Our objective is to identify presentation characteristics which are associated with response and lack of response to a trial of NSAID monotherapy. This is a retrospective single-center cohort study of children diagnosed with sJIA from 2000 to 2014. Patient demographics and disease characteristics were investigated to identify predictors of response to NSAID monotherapy. Eighty-seven children were newly diagnosed with sJIA 2000-2014. Thirteen of the 51 children who received NSAID monotherapy achieved clinically inactive disease (CID) without other medications. Age at presentation (≤8 years old), initial joint count (≤5), and C-reactive protein (CRP) (≤13 mg/dL) at diagnosis were associated with achievement of CID on NSAIDs alone. Physicians were less likely to trial NSAID monotherapy if the patient had either serositis or macrophage activation syndrome (MAS) at diagnosis. Ultimate achievement of CID and time to CID were not significantly affected by whether the patient received a trial of NSAID monotherapy. While a subset of children with sJIA can achieve CID with NSAID monotherapy, we recommend against a trial in patients who are >8 years old, with >5 joints involved, or with CRP > 13 mg/dL. Patients who undergo a trial of NSAID monotherapy should follow up within 2-4 weeks to evaluate for possible need for drug escalation. Clinical trials are necessary to confirm these findings.

Feasibility and efficacy of intraarticular steroids (IAS) in juvenile idiopathic arthritis (JIA).

PubMed

Verma, Sumit; Gupta, Rajiva; Lodha, Rakesh; Kabra, S K

2009-03-01

Thirteen children with juvenile idiopathic arthritis (JIA) were treated with intraarticular steroid injection of triamcilone acetonide as a day care procedure. More than half (53.4%) the children were free of pain, limp and NSAID's use, with improvement in functional score at 12 weeks. No side effects were reported during the period of the study.

Effects of growth hormone treatment on growth in children with juvenile idiopathic arthritis.

PubMed

Simon, D; Bechtold, S

2009-11-01

Several therapeutic trials have been conducted over the past decade to evaluate the role of exogenous growth hormone (GH) as a means of correcting the growth deficiency seen in children with juvenile idiopathic arthritis (JIA). Early studies showed the benefit of GH treatment with respect to final height in patients with JIA. Of 13 patients receiving GH, 84% (11 patients) achieved a final height within their target range compared with only 22% (4 of 18 patients) of untreated patients. There are, however, factors that may limit the statural gains achieved with GH therapy including severe inflammation, severe statural deficiency at GH therapy initiation, long disease duration and delayed puberty. Data on the efficacy of GH replacement therapy in children with JIA and factors that influence the statural growth response will be reviewed. Results from therapeutic trials show that treatment with GH can decrease the statural deficit that occurs during the active phase of JIA, producing an adult height that is close to the genetically determined target height. Copyright 2009 S. Karger AG, Basel.

[Physiotherapy for juvenile idiopathic arthritis].

PubMed

Spamer, M; Georgi, M; Häfner, R; Händel, H; König, M; Haas, J-P

2012-07-01

Control of disease activity and recovery of function are major issues in the treatment of children and adolescents suffering from juvenile idiopathic arthritis (JIA). Functional therapies including physiotherapy are important components in the multidisciplinary teamwork and each phase of the disease requires different strategies. While in the active phase of the disease pain alleviation is the main focus, the inactive phase requires strategies for improving motility and function. During remission the aim is to regain general fitness by sports activities. These phase adapted strategies must be individually designed and usually require a combination of different measures including physiotherapy, occupational therapy, massage as well as other physical procedures and sport therapy. There are only few controlled studies investigating the effectiveness of physical therapies in JIA and many strategies are derived from long-standing experience. New results from physiology and sport sciences have contributed to the development in recent years. This report summarizes the basics and main strategies of physical therapy in JIA.

Facioskeletal changes in children with juvenile idiopathic arthritis

PubMed Central

Twilt, M; Schulten, A J M; Nicolaas, P; Dülger, A; van Suijlekom‐Smit, L W A

2006-01-01

Objective To investigate the facioskeletal morphology in patients with juvenile idiopathic arthritis (JIA) with and without temporomandibular joint (TMJ) involvement. Methods Eighty five patients were included. TMJ involvement was defined by orthopantomogram alterations. Lateral cephalograms were used to determine linear and angular measurements and occlusion. Results Patients regardless of their TMJ status had a 67% chance for retrognathia and a 52% chance for posterior rotation of the mandible and, respectively, 82% and 58% if TMJ involvement were present. Changes were not uniformly distributed among the different subtypes. Conclusion Patients with JIA have an altered facial morphology, especially in the presence of TMJ involvement. PMID:16699052

Leptin concentration in children with juvenile idiopathic arthritis.

PubMed

Maciejewska-Paszek, Izabela; Grochowska-Niedworok, Elżbieta; Siwiec, Andrzej; Dul, Lechosław; Gruenpeter, Anna; Szczerba, Henryk; Irzyniec, Tomasz

2015-01-01

Leptin regulates the organism's immune response. Juvenile idiopathic arthritis (JIA) is a chronic joint disease in children, leading to chronic changes in motor organs. In children with JIA (n = 42) and healthy subjects (n = 28), leptin concentration (LEP), body mass index (BMI), haematocrit (HTC), haemoglobin (HB), morphotic elements (WBC,LYMPH), erythrocyte sedimentation rate (ESR), and ANA Hep-2 antibodies were analysed. JIA group was divided into: children with a longer (51-148 months) (IA) n = 22 and a shorter disease period (2-18 months) (IB) n = 20. Only 58.3% of the IA and 50% of the IB group had ANA Hep-2 confirmed. The ill children had higher and more diversified LYMPH and ESR levels compared to the healthy children. The highest LEP for the IA group was 37.5 ng/cm3, (Me 5.85), for IB - 40.10 ng/cm3, (Me 2.46) as compared to the IC - 3.74 ng/cm3 (Me 2.85), respectively. The average BMI value for the IA group was 16.61 kg/m2, for IC it was 18.91 kg/m2, and the median for IB was 15.89 kg/m2. Children with BMI values < 23 kg/m2 from the IA and IB group had a reduction in LEP as compared to control group (p = 0.04). The relationship between the illness and LEP diversification per BMI unit was found in both groups. Children with a shorter illness period had higher LEP differentiation per BMI unit compared to the healthy children. Children with juvenile idiopathic arthritis with BMI < 23 kg/m2 had lower leptin concentrations than healthy subjects. Ill children with a shorter-term disease had a higher diversification of leptin concentration per BMI unit as compared to healthy controls.

Adalimumab plus Methotrexate for Uveitis in Juvenile Idiopathic Arthritis.

PubMed

Ramanan, Athimalaipet V; Dick, Andrew D; Jones, Ashley P; McKay, Andrew; Williamson, Paula R; Compeyrot-Lacassagne, Sandrine; Hardwick, Ben; Hickey, Helen; Hughes, Dyfrig; Woo, Patricia; Benton, Diana; Edelsten, Clive; Beresford, Michael W

2017-04-27

Adalimumab, a fully human anti-tumor necrosis factor α monoclonal antibody, is effective in the treatment of juvenile idiopathic arthritis (JIA). We tested the efficacy of adalimumab in the treatment of JIA-associated uveitis. In this multicenter, double-blind, randomized, placebo-controlled trial, we assessed the efficacy and safety of adalimumab in children and adolescents 2 years of age or older who had active JIA-associated uveitis. Patients who were taking a stable dose of methotrexate were randomly assigned in a 2:1 ratio to receive either adalimumab (at a dose of 20 mg or 40 mg, according to body weight) or placebo, administered subcutaneously every 2 weeks. Patients continued the trial regimen until treatment failure or until 18 months had elapsed. They were followed for up to 2 years after randomization. The primary end point was the time to treatment failure, defined according to a multicomponent intraocular inflammation score that was based on the Standardization of Uveitis Nomenclature criteria. The prespecified stopping criteria were met after the enrollment of 90 of 114 patients. We observed 16 treatment failures in 60 patients (27%) in the adalimumab group versus 18 treatment failures in 30 patients (60%) in the placebo group (hazard ratio, 0.25; 95% confidence interval [CI], 0.12 to 0.49; P<0.0001 [the prespecified stopping boundary]). Adverse events were reported more frequently in patients receiving adalimumab than in those receiving placebo (10.07 events per patient-year [95% CI, 9.26 to 10.89] vs. 6.51 events per patient-year [95% CI, 5.26 to 7.77]), as were serious adverse events (0.29 events per patient-year [95% CI, 0.15 to 0.43] vs. 0.19 events per patient-year [95% CI, 0.00 to 0.40]). Adalimumab therapy controlled inflammation and was associated with a lower rate of treatment failure than placebo among children and adolescents with active JIA-associated uveitis who were taking a stable dose of methotrexate. Patients who received adalimumab

[Evidence and consensus based treatment guidelines 2010 for juvenile idiopathic arthritis by the German Society of Paediatric Rheumatology].

PubMed

Dueckers, G; Guellac, N; Arbogast, M; Dannecker, G; Foeldvari, I; Frosch, M; Ganser, G; Heiligenhaus, A; Horneff, G; Illhardt, A; Krauspe, R; Markus, B; Michels, H; Schneider, M; Singendonk, W; Sitter, H; Spamer, M; Wagner, N; Niehues, T

2011-11-01

Treatment of Juvenile Idiopathic Arthritis (JIA) has improved quality of life in children and adolescents with JIA. Standardisation of care offers the chance to improve the quality of care of those patients. New studies have been published after completion of our last treatment guideline (2007). An updated consensus process is mandatory. A systematic literature analysis in PUBMED (key words: juvenile idiopathic (rheumatoid) arthritis, therapy; limits: humans, published in the last 3 years, all child 0-18 years, clinical trial) revealed 17 relevant studies. Studies relating to diagnosis of JIA, Uveitis, vaccination, transition were excluded. Representatives nominated by scientific societies and organisations were invited to consensus conferences which were hosted by a professional moderator. The following societies were invited: Berufsverband der Kinder- und Jugendärzte (BVKJ), Deutsche Gesellschaft für Kinder- und Jugendmedizin (DGKJ), Deutsche Gesellschaft für Rheumatologie (DGRh), Deutsche Ophthalmologische Gesellschaft (DOG), Deutsche Rheuma-Liga Bundesverband, Verein zur Förderung und Unterstützung rheumatologisch erkrankter Kinder und deren Eltern, Vereinigung für Kinderorthopädie, Zentraler Verband der Physiotherapeuten und Krankengymnasten (ZVK). Consensus conferences were each attended by more than 95% of the nominated representatives. Consensus statements were confirmed by nominal group technique and Delphi method. Updated consensus statements regarding drug therapy, symptomatic and surgical management of JIA were compiled and judged strictly by the criteria of Evidence-Based Medicine (EBM). © Georg Thieme Verlag KG Stuttgart · New York.

Handwriting difficulties in juvenile idiopathic arthritis: a pilot study.

PubMed

Haberfehlner, Helga; Visser, Bart; Daffertshofer, Andreas; van Rossum, Marion Aj; Roorda, Leo D; van der Leeden, Marike; Dekker, Joost; Hoeksma, Agnes F

2011-01-01

The aim of the present study was to describe handwriting difficulties of primary school children with juvenile idiopathic arthritis (JIA), and to investigate possible correlations with hand function and writing performance. In a cross-sectional approach, 15 children with JIA and reported handwriting difficulties were included together with 15 healthy matched controls. Impairments (signs of arthritis or tenosynovitis, reduced grip force and limited range of motion of the wrist (wrist-ROM)), activity limitations (reduced quality and speed of handwriting, pain during handwriting), and participation restrictions (perceived handwriting difficulties at school) were assessed and analysed. Although selected by the presence of handwriting difficulties, the majority of the JIA children (73%) had no active arthritis of the writing hand, and only minor hand impairments were found. Overall, the JIA children performed well during the short handwriting test, but the number of letters they wrote per minute decreased significantly during the 5-minute test, compared to the healthy controls. JIA patients had significantly higher pain scores on a 100 mm Visual Analogue Scale, compared to the healthy controls. The actual presence of arthritis, and limitation in grip force and wrist-ROM did not correlate with reported participation restrictions with regard to handwriting at school. The JIA children reported pain during handwriting, and inability to sustain handwriting for a longer period of time. The results of this pilot study show that JIA children with handwriting difficulties, experience their restrictions mainly through pain and the inability to sustain handwriting for a longer period of time. No correlations could be found with impairments.

Orofacial symptoms related to temporomandibular joint arthritis in juvenile idiopathic arthritis: smallest detectable difference in self-reported pain intensity.

PubMed

Stoustrup, Peter; Kristensen, Kasper D; Verna, Carlalberta; Küseler, Annelise; Herlin, Troels; Pedersen, Thomas K

2012-12-01

Temporomandibular joint (TMJ) inflammation in patients with juvenile idiopathic arthritis (JIA) may lead to mandibular growth disturbances and interfere with optimal joint and muscle function. Orofacial symptoms are common clinical findings in relation to TMJ arthritis in adolescence. Knowledge about their clinical manifestation is important for TMJ arthritis diagnosis, treatment choice, and outcome evaluation. The aim of our prospective observational study was to evaluate and describe the frequency, the main complaints, and the localization of TMJ arthritis-related orofacial symptoms. The smallest detectable differences (SDD) for minimal, average, and maximal pain were estimated. Thirty-three patients with JIA and arthritis-related orofacial symptoms in relation to 55 affected TMJ were included in our questionnaire study (mean age 14.11 yrs). Calculation of the SDD was based on a duplicate assessment 45 min after the first questionnaire was completed. The majority of the patients had common orofacial symptoms during mastication and maximal mouth opening procedures. Persistent orofacial symptoms were rare. The TMJ area in combination with the masseter muscle region was the orofacial region where symptoms were most common. The SDD for minimal, average, and maximal pain were between 10 and 14 mm on a visual analog scale. Our study offers new knowledge about TMJ arthritis-related orofacial symptoms that may aid diagnosis and clinical decision-making. We suggest that TMJ arthritis-related orofacial symptoms could be understood as products of the primary TMJ inflammation in combination with secondary myogenic and functional issues.

Juvenile Arthritis

MedlinePlus

Juvenile arthritis (JA) is arthritis that happens in children. It causes joint swelling, pain, stiffness, and loss of motion. It can affect any joint, but ... of JA that children get is juvenile idiopathic arthritis. There are several other forms of arthritis affecting ...

25-hydroxyvitamin D levels and juvenile idiopathic arthritis: is there an association with disease activity?

USDA-ARS?s Scientific Manuscript database

To examine the association between serum levels of 25-hydroxyvitamin D [25(OH)D] and disease activity in juvenile idiopathic arthritis (JIA), to determine the prevalence of vitamin D (VD) deficiency [25(OH)D=19 ng/ml] and insufficiency [25(OH)D 20-29 ng/ml], and to determine factors associated with ...

When a patient suspected with juvenile idiopathic arthritis turns out to be diagnosed with an infectious disease - a review of Lyme arthritis in children.

PubMed

Orczyk, Krzysztof; Świdrowska-Jaros, Joanna; Smolewska, Elżbieta

2017-05-08

The Lyme arthritis is a common manifestation of infection with Borrelia burgdorferi spirochete. Despite its infectious background, the inflammation clinically and histopatologically resembles juvenile idiopathic arthritis. As it affects a considerable number of Lyme disease patients, it should be routinely considered in differential diagnosis. Development of arthritis is partially dependent on spirochetal factors, including the ribosomal spacer type and the sequence of outer surface protein C. Immunological background involves Th1-related response, but IL-17 provides an additional route of developing arthritis. Autoimmune mechanisms may lead to antibiotic-refractory arthritis. The current diagnostic standard is based on a 2-step testing: ELISA screening and immunoblot confirmation. Other suggested methods contain modified two-tier test with C6 ELISA instead of immunoblot. An initial 28-day course of oral antibiotics (doxycycline, cefuroxime axetil or amoxicillin) is a recommended treatment. Severe cases require further anti-inflammatory management. Precise investigation of new diagnostic and therapeutic approaches is advisable.

Utility of corticosteroid injection for temporomandibular arthritis in children with juvenile idiopathic arthritis.

PubMed

Arabshahi, Bita; Dewitt, Esi Morgan; Cahill, Ann Marie; Kaye, Robin D; Baskin, Kevin M; Towbin, Richard B; Cron, Randy Q

2005-11-01

To assess the effects of computed tomography (CT)-guided injection of corticosteroid into the temporomandibular joint (TMJ) in children with juvenile idiopathic arthritis (JIA) and clinical and magnetic resonance imaging (MRI) evidence of TMJ inflammation. Twenty-three children ages 4-16 years with JIA and MRI evidence of TMJ inflammation received CT-guided TMJ injections of corticosteroid (triamcinolone acetonide [n = 16] or triamcinolone hexacetonide [n = 7]). Jaw pain or dysfunction and maximal incisal opening (MIO) distance were assessed before and after injection. Fourteen patients had followup MRI studies of the TMJ 6-12 months after injection. Of the 13 patients with symptoms of jaw pain prior to corticosteroid treatment, 10 (77%) had complete resolution of pain (P < 0.05). Prior to corticosteroid injection, MIO in all 23 patients was below age-matched normal values. After injection, the MIO was improved by at least 0.5 cm in 10 patients (43%) (P = 0.0017). Patients under 6 years of age at the time of injection showed the best response, with a postinjection MIO similar to that in age-matched controls (P = 0.2267). There was involvement of 23 TMJs in the 14 patients who had followup MRI studies; resolution of effusions was observed in 11 (48%) of the TMJs. Other than short-term facial swelling in 2 patients, there were no side effects. The majority of children with symptomatic TMJ arthritis improved after intraarticular corticosteroid injection. Approximately half the patients experienced significant improvement in MIO and TMJ effusion. These data suggest that corticosteroid injection may be a useful procedure for the prevention and treatment of morbidities associated with TMJ arthritis in JIA.

Access to pediatric rheumatology care for Juvenile Idiopathic Arthritis in the United Arab Emirates.

PubMed

Khawaja, Khulood; Al-Maini, Mustafa

2017-05-16

This study looks at access to care for Juvenile Idiopathic Arthritis through pediatric rheumatology in the UAE, as an example of multi-ethnic society. Patients with a diagnosis of Juvenile idiopathic arthritis were identified through the hospital electronic medical records system from January 1st 2011 to December 31st 2014. All residents of the United Arab Emirates hold an Emirates identity card. We divided our patients into two groups: Emirati-Emirates, who are native Emirati children and hold the Emirati nationality, as stated on their Emirates identity card, and who therefore have full, comprehensive access to free medical care; and non-Emirati-Emirates, who represent other nationalities, as stated on their Emirates identity card. The primary objective of this study is to look at access to care for Juvenile idiopathic arthritis through pediatric rheumatology in the two groups. The secondary objective is to look at the effect of having multiple types of healthcare insurance coverage on access to biologics. A retrospective review was carried out. Sixty-six patients with JIA identified: 33 Emirates and 33 non-Emirates. For Emirates, the mean time from onset to first appointment with pediatric rheumatologist and diagnosis is 9 months (range: 1-48), and for non-Emirates is 12.4 months (range: 1-96). Among the Emirates, 10 patients are currently on biologic with methotrexate. Among the non-Emirates, 15 are on biologic with methotrexate. Among the Emirates, 12 are currently in remission while on treatment, as are 10 non-Emirates. Regarding disability, one Emirati patient has blindness secondary to noncompliance while under previous treatment. One Non-Emirati developed joint deformities due to periods of noncompliance and no follow up. Delay in presentation to pediatric rheumatology has been identified as an important factor in our population, which is multi-cultural and multi-ethnic. Type of health care insurance cover did not affect number of patients getting

Coronary artery abnormalities in children with systemic-onset juvenile idiopathic arthritis.

PubMed

Lefèvre-Utile, Alain; Galeotti, Caroline; Koné-Paut, Isabelle

2014-05-01

Still's disease (Systemic-onset Juvenile Idiopathic Arthritis: SoJIA) is characterised by high-spiking daily fevers, arthritis and evanescent rashes. Diagnosis of Still's disease is often challenging. Infectious diseases and other inflammatory conditions, especially in young children, Kawasaki disease may look similar. Clinicians often rely on echocardiographic evidence of coronary artery abnormalities to differentiate between Kawasaki disease and Still's disease. Coronary artery dilation would typically favour the diagnosis of Kawasaki disease. We present four children with Still's disease and coronary artery abnormalities who were initially misdiagnosed as Kawasaki disease. The first patient had pericarditis and an irregular wall of the left coronary artery, without dilation on echocardiography. The second patient had a left coronary artery dilatation and a pericarditis. The third patient had thickened left coronary artery walls, and the fourth patient had a hyperechogenicity of the left and right coronary arteries. They received IVIG without success. The diagnosis of Still's disease was made secondary with evidence of persistent arthritis. All but one patient finally needed biologic treatments. Coronary abnormalities may be observed during various febrile conditions and do not exclude the diagnosis of Still's disease. Copyright © 2013 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

The role of heme oxygenase-1 in systemic-onset juvenile idiopathic arthritis.

PubMed

Takahashi, Akitaka; Mori, Masaaki; Naruto, Takuya; Nakajima, Shoko; Miyamae, Takako; Imagawa, Tomoyuki; Yokota, Shumpei

2009-01-01

We have determined the serum levels of heme oxygenase-1 (HO-1) in 56 patients with systemic-onset juvenile idiopathic arthritis (s-JIA) and compared these with serum HO-1 levels in healthy controls and patients with other pediatric rheumatic diseases. Serum HO-1 levels were measured by the sandwich enzyme-linked immunosorbent assay. The mean serum HO-1 level in s-JIA patients during the active phase was 123.6 +/- 13.83 ng/ml, which was significantly higher than that in patients with polyarticular juvenile idiopathic arthritis (p-JIA), Kawasaki disease, systemic lupus erythematosus or mixed connective tissue disease (P < 0.0005). The serum levels of HO-1, cytokines and cytokine receptors in patients with s-JIA were also assessed at both the active and inactive phases. The serum HO-1 level in patients with s-JIA in the active phase was found to be significantly greater than that in patients with the disease in the inactive phase (P < 0.0001). An assessment of the relationships between serum HO-1 levels and other laboratory parameters or cytokines in patients with s-JIA did not reveal any strong correlations. These results suggest that the serum level of HO-1 may be a useful marker for the differential diagnosis of s-JIA. Further study will be necessary to elucidate the mechanism of HO-1 production and to clarify the role of HO-1 in the disease process.

Recommendations for the Use of Ultrasound and Magnetic Resonance in Patients With Spondyloarthritis, Including Psoriatic Arthritis, and Patients With Juvenile Idiopathic Arthritis.

PubMed

Uson, Jacqueline; Loza, Estibaliz; Möller, Ingrid; Acebes, Carlos; Andreu, Jose Luis; Batlle, Enrique; Bueno, Ángel; Collado, Paz; Fernández-Gallardo, Juan Manuel; González, Carlos; Jiménez Palop, Mercedes; Lisbona, María Pilar; Macarrón, Pilar; Maymó, Joan; Narváez, Jose Antonio; Navarro-Compán, Victoria; Sanz, Jesús; Rosario, M Piedad; Vicente, Esther; Naredo, Esperanza

To develop evidence-based recommendations on the use of ultrasound (US) and magnetic resonance imaging in patients with spondyloarthritis, including psoriatic arthritis, and juvenile idiopathic arthritis. Recommendations were generated following a nominal group technique. A panel of experts (15 rheumatologists and 3 radiologists) was established in the first panel meeting to define the scope and purpose of the consensus document, as well as chapters, potential recommendations and systematic literature reviews (we used and updated those from previous EULAR documents). A first draft of recommendations and text was generated. Then, an electronic Delphi process (2 rounds) was carried out. Recommendations were voted from 1 (total disagreement) to 10 (total agreement). We defined agreement if at least 70% of participants voted≥7. The level of evidence and grade or recommendation was assessed using the Oxford Centre for Evidence Based Medicine levels of evidence. The full text was circulated and reviewed by the panel. The consensus was coordinated by an expert methodologist. A total of 12 recommendations were proposed for each disease. They include, along with explanations of the validity of US and magnetic resonance imaging regarding inflammation and damage detection, diagnosis, prediction (structural damage progression, flare, treatment response, etc.), monitoring and the use of US guided injections/biopsies. These recommendations will help clinicians use US and magnetic resonance imaging in patients with spondyloarthritis and juvenile idiopathic arthritis. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

HLA B27 typing in 511 children with juvenile idiopathic arthritis from India.

PubMed

Srivastava, Rajni; Phatak, Sanat; Yadav, Akhilesh; Bajpai, Preeti; Aggarwal, Amita

2016-10-01

The enthesitis-related arthritis (ERA) category of juvenile idiopathic arthritis (JIA) is the most common category in India. HLA B27 has a high prevalence in ERA, and ILAR classification includes it in exclusion criteria for other categories, but due to its cost, it is not routinely done. We undertook this study to assess the prevalence of HLA B27 in ERA and other groups of juvenile arthritis in India. Consecutive patients of JIA ERA and select patients from other categories were recruited from a single tertiary care hospital over a span of 3 years. HLA B27 was tested using PCR. Five hundred and eleven children were studied: 312 had ERA, and 199 had other categories (29 oligoarthritis, 107 polyarthritis, 44 systemic onset JIA, 9 psoriatic arthritis and 10 undifferentiated). The prevalence of HLA B27 was highest in the ERA group (87 %) and correlated with the presence of sacroiliitis. Prevalence was 10.3 % in oligoarthritis, 16 % in polyarticular rheumatoid factor (RF)-positive arthritis, 26 % in RF-negative polyarticular arthritis, 66 % in psoriatic arthritis and 40 % in the unclassified and 0 % in systemic onset category. Twenty-seven children had a change in category of JIA as per ILAR owing to HLA B27 testing positive, most commonly in the RF-negative polyarthritis group. Only six of these had clinical features suggestive of Spondyloarthropathy. There is high prevalence of HLA B27 in ERA. Though HLA B27 testing helps in correct classification, a minority of these patients have features suggestive of spondyloarthropathy like back pain, enthesitis or sacroiliitis.

Juvenile idiopathic arthritis-associated uveitis.

PubMed

Clarke, Sarah L N; Sen, Ethan S; Ramanan, Athimalaipet V

2016-04-27

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood, with JIA-associated uveitis its most common extra-articular manifestation. JIA-associated uveitis is a potentially sight-threatening condition and thus carries a considerable risk of morbidity. The aetiology of the condition is autoimmune in nature with the predominant involvement of CD4(+) T cells. However, the underlying pathogenic mechanisms remain unclear, particularly regarding interplay between genetic and environmental factors. JIA-associated uveitis comes in several forms, but the most common presentation is of the chronic anterior uveitis type. This condition is usually asymptomatic and thus screening for JIA-associated uveitis in at-risk patients is paramount. Early detection and treatment aims to stop inflammation and prevent the development of complications leading to visual loss, which can occur due to both active disease and burden of disease treatment. Visually disabling complications of JIA-associated uveitis include cataracts, glaucoma, band keratopathy and macular oedema. There is a growing body of evidence for the early introduction of systemic immunosuppressive therapies in order to reduce topical and systemic glucocorticoid use. This includes more traditional treatments, such as methotrexate, as well as newer biological therapies. This review highlights the epidemiology of JIA-associated uveitis, the underlying pathogenesis and how affected patients may present. The current guidelines and criteria for screening, diagnosis and monitoring are discussed along with approaches to management.

Pathogenesis of systemic inflammatory diseases in childhood: "Lessons from clinical trials of anti-cytokine monoclonal antibodies for Kawasaki disease, systemic onset juvenile idiopathic arthritis, and cryopyrin-associated periodic fever syndrome".

PubMed

Yokota, Shumpei; Kikuchi, Masako; Nozawa, Tomo; Kanetaka, Taichi; Sato, Tomomi; Yamazaki, Kazuko; Sakurai, Nodoka; Hara, Ryoki; Mori, Masaaki

2015-01-01

Inflammation has often been considered to be a nonspecific response and to play a bridging role in the activation of adaptive immunity. However, it is now accepted that inflammation is the product of an independent innate immune system closely linked to the adaptive immune system. The key mediators of inflammation are inflammatory cytokines, as determined by multiple lines of evidence both in vitro and in vivo. Due to the crucial role of inflammatory cytokines in the pathogenesis of autoimmune disorders, anti-cytokine treatment has been developed as a therapy for rheumatoid arthritis, juvenile idiopathic arthritis (JIA), and inflammatory bowel diseases. We recently completed several clinical trials of anti-cytokine treatment for children with systemic inflammatory diseases: anti-IL-6 receptor monoclonal antibody (tocilizumab) for children with two subtypes of JIA (poly-JIA and systemic JIA), anti-TNF-α monoclonal antibody (infliximab) for children with Kawasaki disease, and anti-IL-1-β monoclonal antibody (canakinumab) for children with cryopyrin-associated periodic syndrome. This review summarizes the basis of inflammation in terms of innate immunity and adaptive immunity in these systemic inflammatory diseases, clinical efficacy, and tolerability of these biologic agents, and attempts to determine the roles of individual inflammatory cytokines in disease pathogenesis.

Juvenile Idiopathic Arthritis in Olmsted County, Minnesota, 1960-2013.

PubMed

Krause, Megan L; Crowson, Cynthia S; Michet, C John; Mason, Thomas; Muskardin, Theresa Wampler; Matteson, Eric L

2016-01-01

To evaluate the incidence and prevalence of juvenile idiopathic arthritis (JIA) in Olmsted County, Minnesota in 1994-2013 and trends in juvenile rheumatoid arthritis (JRA) in 1960-2013. Cases of arthritis in 1994-2013 were identified by diagnosis code with medical chart review to confirm diagnosis separately for JIA and JRA. Overall incidence rates with 95% confidence intervals (95% CIs) were age and sex adjusted to the 2010 US white population. Comparisons were made with an earlier (1960-1993) cohort from this same population. Seventy-one incident cases of JIA in 1994-2013 were identified, with an overall age- and sex-adjusted incidence rate of 10.3 per 100,000 (95% CI 7.9-12.7). Forty-two (59%) were female, with an incidence of 12.4 per 100,000 (95% CI 8.6-16.2), as compared to 8.3 per 100,000 (95% CI 5.2-11.3) in males. The most common subtype was oligoarthritis (63%). The mean ± SD age at diagnosis was 8.2 ± 5.3 years. The prevalence of JIA on January 1, 2000 and January 1, 2010 was 51.0 per 100,000 (95% CI 25.2-76.8) and 57.6 per 100,000 (95% CI 31.0-94.5), respectively. When the annual incidence of JRA was compared over time from 1960 to 2013, there was no significant change in incidence overall; however, the incidence decreased among females (P = 0.003). A cyclic pattern of incidence was observed, with peaks approximately every 10 years. Similar to the findings with regard to incidence, prevalence did not change overall, but decreased among females (P = 0.048). There were 4 deaths in the cohort of JRA patients diagnosed in 1960-2013; the standardized mortality ratio was 1.50 (95% CI 0.41-3.83). Incidence of juvenile arthritis overall in Olmsted County, Minnesota has not changed significantly in the past 53 years. A consistent cyclic pattern was noted. © 2016, American College of Rheumatology.

Methotrexate for the treatment of juvenile idiopathic arthritis: process to approval for JIA indication in Japan

PubMed Central

Naruto, Takuya; Imagawa, Tomoyuki; Murata, Takuji; Takei, Syuji; Tomiita, Minako; Itoh, Yasuhiko; Fujikawa, Satoshi; Yokota, Shumpei

2008-01-01

Methotrexate (MTX), the primary treatment for the articular-type juvenile idiopathic arthritis (JIA), is effective and brings about radiological improvement. Patient compliance is good, and it is recognized that its known side effects, namely, disruption of liver function and induction of pulmonary lesions, are unlikely to be severe at the low MTX doses that are administered. In Japan, MTX was granted approval in 1999 by the then Ministry of Health and Welfare specifically for treating rheumatoid arthritis in adult patients, allowing it be generally used in medical institutions for patients having National Health Insurance. However, in the pediatric field, its use outside the indications has so far been unavoidable, and has been left to the discretion of the physician. Finally, at the present conference, expansion of the indications of MTX for JIA was approved in Japan. It is noteworthy that this expansion of indications was achieved without requiring clinical trials on children sponsored by the pharmaceutical company: it was achieved rather by collecting necessary information through ongoing efforts (including collection and analysis of information about approval status in foreign countries, adequate evidence from the literature, implementation of a clinical use survey in Japan, etc.). It also merits attention that the maximum dose (10 mg/m2) was set on the basis of pharmacokinetic data from children, rather than relying on the dosing method and dose for adults. PMID:18815725

Methotrexate for the treatment of juvenile idiopathic arthritis: process to approval for JIA indication in Japan.

PubMed

Mori, Masaaki; Naruto, Takuya; Imagawa, Tomoyuki; Murata, Takuji; Takei, Syuji; Tomiita, Minako; Itoh, Yasuhiko; Fujikawa, Satoshi; Yokota, Shumpei

2009-01-01

Methotrexate (MTX), the primary treatment for the articular-type juvenile idiopathic arthritis (JIA), is effective and brings about radiological improvement. Patient compliance is good, and it is recognized that its known side effects, namely, disruption of liver function and induction of pulmonary lesions, are unlikely to be severe at the low MTX doses that are administered. In Japan, MTX was granted approval in 1999 by the then Ministry of Health and Welfare specifically for treating rheumatoid arthritis in adult patients, allowing it be generally used in medical institutions for patients having National Health Insurance. However, in the pediatric field, its use outside the indications has so far been unavoidable, and has been left to the discretion of the physician. Finally, at the present conference, expansion of the indications of MTX for JIA was approved in Japan. It is noteworthy that this expansion of indications was achieved without requiring clinical trials on children sponsored by the pharmaceutical company: it was achieved rather by collecting necessary information through ongoing efforts (including collection and analysis of information about approval status in foreign countries, adequate evidence from the literature, implementation of a clinical use survey in Japan, etc.). It also merits attention that the maximum dose (10 mg/m2) was set on the basis of pharmacokinetic data from children, rather than relying on the dosing method and dose for adults.

Prevalence of HLA-B27 antigen in patients with juvenile idiopathic arthritis.

PubMed

Żuber, Zbigniew; Turowska-Heydel, Dorota; Sobczyk, Małgorzata; Chudek, Jerzy

2015-01-01

Human leukocyte antigen B27 (HLA-B27) is considered as a risk factor for development of juvenile idiopathic arthritis (JIA). The aim of this study was to analyse the prevalence of HLA-B27 antigen in JIA categories and its influence on disease onset and response to conventional therapy. The retrospective analysis included 461 unselected children with JIA hospitalized in a single reference rheumatology centre between July 2007 and June 2012. The diagnosis was based on criteria by the International League of Association for Rheumatology. HLA-B27 was determined in 387 of all patients (84%) by hybridization of the amplified, labelled product to immobilize it on the microarray probe. HLA-B27 antigen was found in 104 of 383 affected children (27.2%), 48 of 206 girls (23.3%), and 56 of 177 boys (31.6%) - most frequently in patients with enthesitis-related arthritis (71%), psoriatic arthritis (50%) and unclassified cases (86.7%). The age of JIA onset was slightly (by 1 year) but significantly different in patients with and without HLA-B27 antigen [11 (8.5-14) vs. 10 (5-13.5) years.; p < 0.001]. The use of disease-modifying antirheumatic drugs (DMARDs) and corticosteroids was more frequently clinically ineffective in HLA-B27 positive than negative patients (23.1% vs. 15.2%; p = 0.09). Patients with polyarthritis, systemic, and psoriatic arthritis more frequently received biological therapy. HLA-B27 positive patients with enthesitis-related arthritis received biological therapy more frequently than HLA-B27 negative ones (20.4% vs. 0, respectively; p = 0.09). HLA-B27 antigen is a strong risk factor for the development of enthesitis-related arthritis, and to a lesser extent for psoriatic arthritis and extended course of oligoarthritis. The presence of this antigen does not affect the disease onset but seems to predict resistance to therapy with disease-modifying drugs and corticosteroids.

Prevalence of HLA-B27 antigen in patients with juvenile idiopathic arthritis

PubMed Central

Turowska-Heydel, Dorota; Sobczyk, Małgorzata; Chudek, Jerzy

2015-01-01

Introduction Human leukocyte antigen B27 (HLA-B27) is considered as a risk factor for development of juvenile idiopathic arthritis (JIA). The aim of this study was to analyse the prevalence of HLA-B27 antigen in JIA categories and its influence on disease onset and response to conventional therapy. Material and methods The retrospective analysis included 461 unselected children with JIA hospitalized in a single reference rheumatology centre between July 2007 and June 2012. The diagnosis was based on criteria by the International League of Association for Rheumatology. HLA-B27 was determined in 387 of all patients (84%) by hybridization of the amplified, labelled product to immobilize it on the microarray probe. Results HLA-B27 antigen was found in 104 of 383 affected children (27.2%), 48 of 206 girls (23.3%), and 56 of 177 boys (31.6%) – most frequently in patients with enthesitis-related arthritis (71%), psoriatic arthritis (50%) and unclassified cases (86.7%). The age of JIA onset was slightly (by 1 year) but significantly different in patients with and without HLA-B27 antigen [11 (8.5–14) vs. 10 (5–13.5) years.; p < 0.001]. The use of disease-modifying antirheumatic drugs (DMARDs) and corticosteroids was more frequently clinically ineffective in HLA-B27 positive than negative patients (23.1% vs. 15.2%; p = 0.09). Patients with polyarthritis, systemic, and psoriatic arthritis more frequently received biological therapy. HLA-B27 positive patients with enthesitis-related arthritis received biological therapy more frequently than HLA-B27 negative ones (20.4% vs. 0, respectively; p = 0.09). Conclusions HLA-B27 antigen is a strong risk factor for the development of enthesitis-related arthritis, and to a lesser extent for psoriatic arthritis and extended course of oligoarthritis. The presence of this antigen does not affect the disease onset but seems to predict resistance to therapy with disease-modifying drugs and corticosteroids. PMID:27407238

Methotrexate-induced nausea in the treatment of juvenile idiopathic arthritis.

PubMed

Falvey, Sonja; Shipman, Lauren; Ilowite, Norman; Beukelman, Timothy

2017-06-19

Methotrexate is the most commonly used disease modifying antirheumatic drug in the treatment of juvenile idiopathic arthritis and can be effective in controlling disease in many patients. A significant proportion of patients experience nausea and vomiting induced by methotrexate therapy, which can lead to decreased quality of life and discontinuation of treatment with methotrexate. Many strategies have been employed in attempts to reduce methotrexate-induced nausea, including folate supplementation, switching from oral to subcutaneous methotrexate, anti-emetic therapy, behavioral therapy, and others. Anticipatory nausea can be difficult to treat, making primary prevention of nausea with anti-emetics an attractive approach. Understanding the prevalence and impact of methotrexate-induced nausea, as well as potentially effective interventions, may help maximize the therapeutic benefits of methotrexate.

Overlap of disease susceptibility loci for rheumatoid arthritis and juvenile idiopathic arthritis

PubMed Central

Hinks, Anne; Eyre, Steve; Ke, Xiayi; Barton, Anne; Martin, Paul; Flynn, Edward; Packham, Jon; Worthington, Jane; Thomson, Wendy

2010-01-01

Background Genome-wide association studies (GWAS) have been extremely successful in the search for susceptibility risk factors for complex genetic autoimmune diseases. As more studies are published, evidence is emerging of considerable overlap of loci between these diseases. In juvenile idiopathic arthritis (JIA), another complex genetic autoimmune disease, the strategy of using information from autoimmune disease GWAS or candidate gene studies to help in the search for novel JIA susceptibility loci has been successful, with confirmed association with two genes, PTPN22 and IL2RA. Rheumatoid arthritis (RA) is an autoimmune disease that shares similar clinical and pathological features with JIA and, therefore, recently identified confirmed RA susceptibility loci are also excellent JIA candidate loci. Objective To determine the overlap of disease susceptibility loci for RA and JIA. Methods Fifteen single nucleotide polymorphisms (SNPs) at nine RA-associated loci were genotyped in Caucasian patients with JIA (n=1054) and controls (n=3531) and tested for association with JIA. Allele and genotype frequencies were compared between cases and controls using the genetic analysis software, PLINK. Results Two JIA susceptibility loci were identified, one of which was a novel JIA association (STAT4) and the second confirmed previously published associations of the TRAF1/C5 locus with JIA. Weak evidence of association of JIA with three additional loci (Chr6q23, KIF5A and PRKCQ) was also obtained, which warrants further investigation. Conclusion All these loci are good candidates in view of the known pathogenesis of JIA, as genes within these regions (TRAF1, STAT4, TNFAIP3, PRKCQ) are known to be involved in T-cell receptor signalling or activation pathways. PMID:19674979

Internet Program for Physical Activity and Exercise Capacity in Children With Juvenile Idiopathic Arthritis: A Multicenter Randomized Controlled Trial.

PubMed

Armbrust, Wineke; Bos, G J F Joyce; Wulffraat, Nico M; van Brussel, Marco; Cappon, Jeannette; Dijkstra, Pieter U; Geertzen, Jan H B; Legger, G Elizabeth; van Rossum, Marion A J; Sauer, Pieter J J; Lelieveld, Otto T H M

2017-07-01

To determine the effects of Rheumates@Work, an internet-based program supplemented with 4 group sessions, aimed at improving physical activity, exercise capacity, health-related quality of life (HRQoL), and participation in children with juvenile idiopathic arthritis. Patients were recruited from 3 pediatric rheumatology centers in The Netherlands for an observer-blinded, randomized controlled multicenter trial. Physical activity level, time spent in rest, light, and moderate-to-vigorous physical activity (MVPA) were recorded in a diary and with an accelerometer, before intervention, after intervention, and at followup after 3 and 12 months (intervention group only). Exercise capacity was assessed using the Bruce treadmill protocol, HRQoL was assessed with the Pediatric Quality of Life Inventory generic core scale, and participation in school and in physical education classes were assessed by questionnaire. The intervention group consisted of 28 children, and there were 21 children in the control group. MVPA , exercise capacity, and participating in school and physical education classes improved significantly in the intervention group. HRQoL improved in the control group. No significant differences were found between groups. The effect of Rheumates@Work on physical activity and exercise capacity lasted during the 12 months of followup. Improvements in physical activity were significantly better for the cohort starting in winter compared to the summer cohort. Rheumates@Work had a positive, albeit small, effect on physical activity, exercise capacity, and participation in school and physical education class in the intervention group. Improvements lasted for 12 months. Participants who started in winter showed the most improvement. Rheumates@Work had no effect on HRQoL. © 2016, American College of Rheumatology.

The importance of an ophthalmologic examination in patients with juvenile idiopathic arthritis.

PubMed

Rodríguez-García, Alejandro

2015-01-01

Uveitis occurs within the first year of arthritis onset in 73% of patients with juvenile idiopathic arthritis (JIA) considered at risk. The intraocular inflammation is characterized by an insidious onset and a silent and chronic clinical course capable of producing significant visual loss due to complications such as: cataract formation, secondary glaucoma, maculopathy and optic neuropathy. The absence of initial signs and symptoms, along with a deficient ophthalmic monitoring produce a delay in diagnosis with serious consequences. It has been estimated that 47% of JIA patients at risk for developing uveitis are legally blind (20/200 or worse) at least in one eye at the time of their first visit to the ophthalmologist. To reduce ocular complications and improve their visual outcome, it is necessary that rheumatologists refer all patients recently diagnosed (within the first month) with JIA for an ophthalmic evaluation, and maintain periodical follow-up visits based on classification and risk category of the disease. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Triamcinolone acetonide and hexacetonide intra-articular treatment of symmetrical joints in juvenile idiopathic arthritis: a double-blind trial.

PubMed

Zulian, F; Martini, G; Gobber, D; Plebani, M; Zacchello, F; Manners, P

2004-10-01

Pharmacokinetic studies have shown that the biological effect of triamcinolone acetonide (TA) is equivalent to that of triamcinolone hexacetonide (TH), if used at double the dosage. In this study we compared the efficacy of intra-articular TA at a dose twice that of TH in symmetrically involved joints, in children with juvenile idiopathic arthritis (JIA). Children with active arthritis and a similar degree of inflammation in two symmetrical joints were enrolled in the study. The symmetry was assessed by both clinical examination and synovial fluid analysis. The dose given was 1 mg/kg up to 40 mg of TH or 2.0 mg/kg up to 80 mg of TA. The identity of injected compound was blinded to the patient and to the physician. Thirty-seven patients, 30 female, seven male, with JIA, entered the study. A total of 86 joints were injected. Twenty-one (53.8%) of the joints injected with TA relapsed first compared with only six (15.4%) of the joints injected with TH. In three (7.7%) relapse occurred simultaneously. Nine (23%) were still in remission after 24-month follow-up. The percentage of joints with lasting remission was higher with TH than with TA (80 vs 47.5% after 12 months and 63.6 vs 32.4% after 24 months, respectively; log rank test P = 0.003). Even when TA is given at higher doses, TH is more effective and should be considered the drug of choice for intra-articular treatment of JIA.

Juvenile Idiopathic Arthritis in the Era of International Cooperation.

PubMed

Uziel, Yosef

2017-01-30

Juvenile idiopathic arthritis (JIA) is the most common chronic disease of childhood. Improved understanding of its pathogenesis has led to international cooperation in clinical studies. Multicenter, international collaborations and research facilitate rapid enrollment of enough patients to enable a variety of studies, including those of epidemiology, diagnostic and classification criteria, genetic disease predisposition, pathogenesis, outcomes, and treatment protocols. In the last 20 years, the vision of the Pediatric Rheumatology International Trial Organization (PRINTO) has become a reality of worldwide collaboration in pediatric rheumatology research, including North American and European research groups. Major advances have been made in treating systemic JIA and its main complication, macrophage-activating syndrome (MAS). Single Hub and Access Point to Pediatric Rheumatology in Europe (SHARE) is a project of the European Society of Pediatric Rheumatology with the goal of improving clinical care. Based on evidence in the scientific literature, position papers regarding optimal clinical approaches and care have been published. Formal, validated assessment tools to evaluate response to treatment have been developed. Recommendations have been established to encourage international research collaborations, especially in light of major advances achieved in the genetics of pediatric rheumatologic diseases and the need to share biological samples among different countries and continents. Every participating country has disease information available for patients and families. Additionally, educational programs and updated syllabi for pediatric rheumatology have been written to promote similar, high-level academic training in different countries. These efforts have resulted in significant improvements in treatment and in patient prognosis. However, improved cooperation is needed to enhance research with biological and genetic samples. The Israeli Research Group for

Association of systemic-onset juvenile idiopathic arthritis and celiac disease - a case report.

PubMed

Michelin, Cintia Maria; Aikawa, Nadia Emi; Diniz, João Carlos; Jesus, Adriana Almeida; Koda, Yu Kar; Silva, Clovis Artur

2011-01-01

In a 28-year period, 5508 patients were followed at our Paediatric Rheumatology Division and 712 (13%) patients had juvenile idiopathic arthritis (JIA) (ILAR criteria). One (0.14%) of them had association with celiac disease (CD), with predominance of gastrointestinal manifestations and this case was described herein. A 10-years-old female patient was hospitalized with persistent fever, weight loss, asthenia, anorexia and an evanescent pink macular rash. After one week, she presented arthritis of left knee and ankle with duration of 75 days. The initial laboratory exams revealed anemia and elevation of inflammatory markers. Immunological tests were positive for anti-endomysial antibodies IgA and anti-thyroglobulin antibody. The diagnosis of systemic JIA was established and indomethacin (2.0 mg/kg/day) was started with improvement of arthritis. The patient evolved with vomiting, diarrhea and abdominal pain and upper gastrointestinal barium study showed areas of small bowel dilatation and thickening of folds, suggestive of malabsorption syndrome. Colonoscopy was normal and small intestinal biopsy was compatible with CD. We reported a case of a rare association of early diagnosis of systemic JIA occurring simultaneously with CD. This study reinforces the importance of taking into account the possible association of organ-specific autoimmune diseases during JIA course.

Glucocorticoids in the management of systemic juvenile idiopathic arthritis.

PubMed

Vannucci, Gaia; Cantarini, Luca; Giani, Teresa; Marrani, Edoardo; Moretti, Davide; Pagnini, Ilaria; Simonini, Gabriele; Cimaz, Rolando

2013-10-01

Glucocorticoids have been the mainstay of treatment for many years in systemic-onset juvenile idiopathic arthritis (sJIA), causing important side effects and some difficulties in the management of this disease. Until the introduction of biologic agents, oral glucocorticoids were used to control fever and other systemic features for several months or even years if systemic manifestations persisted. Nowadays, clinicians have valid alternatives that have revolutionized the natural history of sJIA. Biologic agents, such as the interleukin-1 inhibitors anakinra and the more recent canakinumab, or the interleukin-6 inhibitor tocilizumab, have improved the prognosis of this debilitating disease. Glucocorticoids still have to be considered at the onset of disease when a non-steroidal anti-inflammatory drug therapy fails or when there are life-threatening complications such as severe anemia or pericarditis, or macrophage activation syndrome. Local (intra-articular) triamcinolone hexacetonide is the treatment of choice for arthritis limited to one joint or a few joints in patients without systemic activity. To date, there is still great heterogeneity in the management of sJIA patients, but in recent years there have been attempts to design algorithms and treatment protocols for glucocorticoids, disease-modifying anti-rheumatic drugs, and biologic agents. This review provides an overview of the current knowledge of glucocorticoid therapy in sJIA, comments on recently published recommendations, and gives practical support to the clinician for management of this disease.

Retrospective Study Evaluating Treatment Decisions and Outcomes of Childhood Uveitis Not Associated with Juvenile Idiopathic Arthritis.

PubMed

Sardar, Elham; Dusser, Perrine; Rousseau, Antoine; Bodaghi, Bahram; Labetoulle, Marc; Koné-Paut, Isabelle

2017-07-01

To evaluate treatment, ocular complications and outcomes of children with pediatric uveitis not associated with juvenile idiopathic arthritis. This was a retrospective chart review of pediatric uveitis in children under 16 years of age, recruited from the pediatric rheumatology department at Bicêtre Hospital from 2005 to 2015. Patients with juvenile idiopathic arthritis-associated and infectious uveitis were excluded. We used the Standardization of Uveitis Nomenclature Working Group to classify uveitis, disease activity, and treatment end points. We enrolled 56 patients and 102 affected eyes. The mean age at diagnosis was 10 ± 3.5 years (range 3-15), and the mean follow-up 4.2 ± 3.3 years (1-15). The main diagnoses were idiopathic (55%), Behçet disease (15%), and sarcoidosis (5%). The main localization was panuveitis in 44 of 102 eyes (43%). Corticosteroid sparing treatment was needed in 62 of 102 eyes (60%). Second-line therapies included methotrexate and azathioprine, and the third-line therapy was a biologic agent, mainly infliximab, in 33 of 102 eyes (32%). Infliximab achieved uveitis inactivity in 14 of 18 eyes (80%), in all etiologies. Severe complications were present in 68 of 102 eyes (67%). The most common were synechiae 33% of eyes, cataract (20%), and macular edema (25%). Of these, 37% were present at diagnosis. Remission was achieved in 22 of 102 eyes (21%). Conventional therapies were insufficient to treat many of the cases of posterior or panuveitis. This study underlines the need for earlier and more aggressive treatment and antitumor necrosis factor-α therapy was rapidly efficient in most cases of refractory uveitis. Copyright © 2017 Elsevier Inc. All rights reserved.

[Magnetic resonance imaging in juvenile idiopathic arthritis: peculiarities of imaging children].

PubMed

Navallas, M; Rebollo Polo, M; Riaza, L; Muchart López, J; Maristany, T

2013-09-01

The term juvenile idiopathic arthritis (JIA) encompasses a heterogeneous group of arthritides with no known cause that begin before the age of 16 years and persist for at least 6 weeks. In recent decades, imaging techniques have acquired a fundamental role in the diagnosis and follow-up of JIA, owing to the unification of the different criteria for classification, which has strengthened the research in this field, and to the development of disease-modifying antirheumatic drugs. In this article, we briefly explain what JIA is. Moreover, we describe the role and limitations of plain-film radiography, ultrasonography, and magnetic resonance imaging (MRI). Finally, we review the MRI protocol and findings, and we comment on the differential diagnosis. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

Biomarkers in systemic juvenile idiopathic arthritis: a comparison with biomarkers in cryopyrin-associated periodic syndromes.

PubMed

Nirmala, Nanguneri; Grom, Alexei; Gram, Hermann

2014-09-01

This review summarizes biomarkers in systemic juvenile idiopathic arthritis (sJIA). Broadly, the markers are classified under protein, cellular, gene expression and genetic markers. We also compare the biomarkers in sJIA to biomarkers in cryopyrin-associated periodic syndrome (CAPS). Recent publications showing the similarity of clinical response of sJIA and CAPS to anti-interleukin 1 therapies prompted a comparison at the biomarker level. sJIA traditionally is classified under the umbrella of juvenile idiopathic arthritis. At the clinical phenotypic level, sJIA has several features that are more similar to those seen in CAPS. In this review, we summarize biomarkers in sJIA and CAPS and draw upon the various similarities and differences between the two families of diseases. The main differences between sJIA and CAPS biomarkers are genetic markers, with CAPS being a family of monogenic diseases with mutations in NLRP3. There have been a small number of publications describing cellular biomarkers in sJIA with no such studies described for CAPS. Many of the protein marker's characteristics of sJIA are also seen to characterize CAPS. The gene expression data in both sJIA and CAPS show a strong upregulation of innate immunity pathways. In addition, we describe a strong similarity between sJIA and CAPS at the gene expression level in which several genes that form a part of the erythropoiesis signature are upregulated in both sJIA and CAPS.

Influence of past breast feeding on pattern and severity of presentation of juvenile idiopathic arthritis.

PubMed

Hyrich, Kimme L; Baildam, Eileen; Pickford, Hannah; Chieng, Alice; Davidson, Joyce E; Foster, Helen; Gardner-Medwin, Janet; Wedderburn, Lucy R; Thomson, Wendy

2016-04-01

This analysis aimed to study the influence of breast feeding on the pattern and severity of juvenile idiopathic arthritis (JIA) at presentation. The association between ever versus never breast feeding and disease severity at onset was compared in 923 children with JIA recruited to the UK Childhood Arthritis Prospective Study at first presentation to rheumatology. Fifty six per cent of children were ever breast fed (median 3.7 months). Breastfed children reported a lower median age at onset, a lower Childhood Health Assessment Questionnaire (CHAQ), a measure of disease severity, lower parent general evaluation scores and lower pain at presentation. There was a trend towards a higher proportion of breastfed children with rheumatoid factor-negative polyarthritis, but lesser enthesitis-related and psoriatic arthritis. There was a statistically significant inverse association between breast feeding and high CHAQ, even after adjusting for differences in socioeconomic status (adjusted OR 0.61 (95% CI 0.39 to 0.95)). Further work to understand the reasons behind these associations is required. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Exercise Therapy in Juvenile Idiopathic Arthritis: A Systematic Review and Meta-Analysis.

PubMed

Kuntze, Gregor; Nesbitt, Colleen; Whittaker, Jackie L; Nettel-Aguirre, Alberto; Toomey, Clodagh; Esau, Shane; Doyle-Baker, Patricia K; Shank, Jena; Brooks, Julia; Benseler, Susanne; Emery, Carolyn A

2018-01-01

To conduct a systematic review to evaluate the efficacy of exercise interventions in improving outcomes across domains of functioning and disability in children and adolescents with juvenile idiopathic arthritis (JIA). Seven electronic databases were systematically searched up to November 16, 2016. Original data, analytic prospective design, physical therapy-led exercise intervention evaluation, children and adolescents with JIA, and assessment of functional, structural, activity, participation, or quality of life outcomes. Two authors screened search results, and discrepancies were resolved by consensus. Of 5037 potentially relevant studies, 9 randomized controlled trials and 1 cohort study were included and scored. Study quality (Downs and Black quality assessment tool) and level of evidence (Oxford Centre of Evidence-Based Medicine model) were assessed and meta-analysis conducted where appropriate. Alternatively, a descriptive summary approach was chosen. All randomized controlled trials were moderate-quality intervention studies (level 2b evidence; median Downs and Black score, 20 out of 32; range, 15-27). Interventions included aquatic, strengthening, proprioceptive, aerobic, and Pilates exercises. Pediatric activity capacity (Child Health Assessment Questionnaire) improved with exercise (mean difference, .45; 95% confidence interval, .05-.76). Furthermore, descriptive summaries indicated improved activity capacity, body function and structure (pain and muscle strength), and quality of life outcomes. Exercise therapy appears to be well tolerated and beneficial across clinically relevant outcomes in patients with JIA. The paucity of high-quality evidence and study heterogeneity limited the ability to provide conclusive, generalizing evidence for the efficacy of exercise therapy and to provide specific recommendations for clinical practice at this time. Future research evaluating exercise program implementation using validated outcomes and detailed adherence and

Consensus Treatment Plans for New-Onset Systemic Juvenile Idiopathic Arthritis

PubMed Central

DeWitt, Esi Morgan; Kimura, Yukiko; Beukelman, Timothy; Nigrovic, Peter A.; Onel, Karen; Prahalad, Sampath; Schneider, Rayfel; Stoll, Matthew L.; Angeles-Han, Sheila; Milojevic, Diana; Schikler, Kenneth N.; Vehe, Richard K.; Weiss, Jennifer E.; Weiss, Pamela; Ilowite, Norman T.; Wallace, Carol A.

2012-01-01

Objective There is wide variation in therapeutic approaches to systemic juvenile idiopathic arthritis (sJIA) among North American rheumatologists. Understanding the comparative effectiveness of the diverse therapeutic options available for treatment of sJIA can result in better health outcomes. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans and standardized assessment schedules for use in clinical practice to facilitate such studies. Methods Case-based surveys were administered to CARRA members to identify prevailing treatments for new-onset sJIA. A 2-day consensus conference in April 2010 employed modified nominal group technique to formulate preliminary treatment plans and determine important data elements for collection. Follow-up surveys were employed to refine the plans and assess clinical acceptability. Results The initial case-based survey identified significant variability among current treatment approaches for new onset sJIA, underscoring the utility of standardized plans to evaluate comparative effectiveness. We developed four consensus treatment plans for the first 9 months of therapy, as well as case definitions and clinical and laboratory monitoring schedules. The four treatment regimens included glucocorticoids only, or therapy with methotrexate, anakinra or tocilizumab, with or without glucocorticoids. This approach was approved by >78% of CARRA membership. Conclusion Four standardized treatment plans were developed for new-onset sJIA. Coupled with data collection at defined intervals, use of these treatment plans will create the opportunity to evaluate comparative effectiveness in an observational setting to optimize initial management of sJIA. PMID:22290637

Investigation of rheumatoid arthritis susceptibility loci in juvenile idiopathic arthritis confirms high degree of overlap.

PubMed

Hinks, Anne; Cobb, Joanna; Sudman, Marc; Eyre, Stephen; Martin, Paul; Flynn, Edward; Packham, Jonathon; Barton, Anne; Worthington, Jane; Langefeld, Carl D; Glass, David N; Thompson, Susan D; Thomson, Wendy

2012-07-01

Rheumatoid arthritis (RA) shares some similar clinical and pathological features with juvenile idiopathic arthritis (JIA); indeed, the strategy of investigating whether RA susceptibility loci also confer susceptibility to JIA has already proved highly successful in identifying novel JIA loci. A plethora of newly validated RA loci has been reported in the past year. Therefore, the aim of this study was to investigate these single nucleotide polymorphisms (SNP) to determine if they were also associated with JIA. Thirty-four SNP that showed validated association with RA and had not been investigated previously in the UK JIA cohort were genotyped in JIA cases (n=1242), healthy controls (n=4281), and data were extracted for approximately 5380 UK Caucasian controls from the Wellcome Trust Case-Control Consortium 2. Genotype and allele frequencies were compared between cases with JIA and controls using PLINK. A replication cohort of 813 JIA cases and 3058 controls from the USA was available for validation of any significant findings. Thirteen SNP showed significant association (p<0.05) with JIA and for all but one the direction of association was the same as in RA. Of the eight loci that were tested, three showed significant association in the US cohort. A novel JIA susceptibility locus was identified, CD247, which represents another JIA susceptibility gene whose protein product is important in T-cell activation and signalling. The authors have also confirmed association of the PTPN2 and IL2RA genes with JIA, both reaching genome-wide significance in the combined analysis.

Clinical responsiveness of self-report functional assessment measures for children with juvenile idiopathic arthritis undergoing intraarticular corticosteroid injections.

PubMed

Brown, G Ted; Wright, F Virginia; Lang, Bianca A; Birdi, Nina; Oen, Kim; Stephens, Derek; McComas, Joan; Feldman, Brian M

2005-12-15

The Childhood Health Assessment Questionnaire (CHAQ), Juvenile Arthritis Functional Assessment Report (JAFAR), and Juvenile Arthritis Functional Status Index (JASI) are widely used functional measures for juvenile idiopathic arthritis (JIA) that differ in content, format, and completion time. We compared the responsiveness and child-parent agreement of the JAFAR, CHAQ, and JASI in a prospective, multicenter study. Children and adolescents from 5 rheumatology centers were enrolled. Subjects were about to undergo therapy (intraarticular corticosteroid injections [IAS] and methotrexate or hip surgery (MTX/hip]) expected to produce a functional improvement. All subjects were studied before the intervention and at 6 weeks and 6 months posttreatment. At each study visit, the 3 measures were administered in randomized, balanced order to both parents and children. A total of 92 subjects (mean age 12.8 years) were enrolled in the study, 74 of which were in the IAS group. The responsiveness of all 3 measures was moderate to strong. The standardized response mean at 6 weeks for the IAS group on the JAFAR, CHAQ, and JASI was 0.41 (95% confidence interval [95% CI] 0.18, 0.64), 0.70 (95% CI 0.47, 0.93), and 0.36 (95% CI 0.13, 0.59), respectively. The CHAQ was somewhat more responsive to change at 6 weeks (IAS group: relative efficiency 0.34 [JAFAR], 0.27 [JASI]), but less responsive at 6 months (MTX/hip group: relative efficiency 5.1 [JAFAR], 3.9 [JASI]). All 3 questionnaires showed acceptable parent-child agreement, and overall, there were few differences between the 3 questionnaires. The functional outcome measures currently used for JIA are all adequately responsive for use in trials or in the clinic setting. The choice of which measure to use should therefore be based on the time available for completion, the intended clinical/research use, and the depth of content required.

Validity of juvenile idiopathic arthritis diagnoses using administrative health data.

PubMed

Stringer, Elizabeth; Bernatsky, Sasha

2015-03-01

Administrative health databases are valuable sources of data for conducting research including disease surveillance, outcomes research, and processes of health care at the population level. There has been limited use of administrative data to conduct studies of pediatric rheumatic conditions and no studies validating case definitions in Canada. We report a validation study of incident cases of juvenile idiopathic arthritis in the Canadian province of Nova Scotia. Cases identified through administrative data algorithms were compared to diagnoses in a clinical database. The sensitivity of algorithms that included pediatric rheumatology specialist claims was 81-86%. However, 35-48% of cases that were identified could not be verified in the clinical database depending on the algorithm used. Our case definitions would likely lead to overestimates of disease burden. Our findings may be related to issues pertaining to the non-fee-for-service remuneration model in Nova Scotia, in particular, systematic issues related to the process of submitting claims.

Infection-Related Death among Persons with Refractory Juvenile Idiopathic Arthritis

PubMed Central

Lane, Jonathan P.; Wood, Mark; Friswell, Mark; Flood, Terence J.; Foster, Helen E.

2016-01-01

Severe infections are emerging as major risk factors for death among children with juvenile idiopathic arthritis (JIA). In particular, children with refractory JIA treated with long-term, multiple, and often combined immunosuppressive and antiinflammatory agents, including the new biological disease-modifying antirheumatic drugs (DMARDs), are at increased risk for severe infections and death. We investigated 4 persons with JIA who died during 1994–2013, three of overwhelming central venous catheter–related bacterial sepsis caused by coagulase-negative Staphylococus or α-hemolytic Streptococcus infection and 1 of disseminated adenovirus and Epstein-Barr virus infection). All 4 had active JIA refractory to long-term therapy with multiple and combined conventional and biological DMARDs. Two died while receiving high-dose systemic corticosteroids, methotrexate, and after recent exposure to anti–tumor necrosis factor-α biological DMARDs, and 2 during hematopoietic stem cell transplantation procedure. Reporting all cases of severe infections and especially deaths in these children is of paramount importance for accurate surveillance. PMID:27648582

Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis.

PubMed

Oray, Merih; Tuğal-Tutkun, İlknur

2016-04-01

Pediatric uveitis may be a serious health problem because of the lifetime burden of vision loss due to severe complications if the problem is not adequately treated. Juvenile idiopathic arthritis (JIA)-associated uveitis is characterized by insidious onset and potentially blinding chronic anterior uveitis. Periodic ophthalmologic screening is of utmost importance for early diagnosis of uveitis. Early diagnosis and proper immunomodulatory treatment are essential for good visual prognosis. The goal of treatment is to achieve enduring drug-free remission. The choice of therapeutic regimen needs to be tailored to each individual case. One must keep in mind that patients under immunomodulatory treatment should be monitored closely due to possible side effects. Local and systemic corticosteroids have long been the mainstay of therapy; however, long-term corticosteroid therapy should be avoided due to serious side effects. Steroid-sparing agents in the treatment of JIA-associated uveitis include antimetabolites and biologic agents in refractory cases. Among the various immunomodulatory agents, methotrexate is generally the first choice, as it has a well-established safety and efficacy profile in pediatric cases and does not appear to increase the risk of cancer. Other classic immunomodulators that may also be used in combination with methotrexate include azathioprine, mycophenolate mofetil, and cyclosporin A. Biologic agents, primarily tumor necrosis factor alpha inhibitors including infliximab or adalimumab, should be considered in cases of treatment failure with classic immunomodulatory agents.

Biomarkers in Systemic Juvenile Idiopathic Arthritis: A comparison with biomarkers in Cryopyrin Associated Periodic Syndromes

PubMed Central

Nirmala, Nanguneri; Grom, Alexei; Gram, Hermann

2015-01-01

Purpose of review This review summarizes biomarkers in Systemic Juvenile Idiopathic Arthritis (sJIA). Broadly, the markers are classified under protein, cellular, gene expression and genetic markers. We also compare the biomarkers in sJIA to biomarkers in cryopyrin associated periodic syndromes (CAPS). Recent findings Recent publications showing the similarity of clinical response of sJIA and CAPS to anti IL1 therapies prompted a comparison at the biomarker level. Summary sJIA traditionally is classified under the umbrella of juvenile idiopathic arthritis. At the clinical phenotypic level, sJIA has several features that are more similar to those seen in Cryopyrin Associated Periodic Syndromes (CAPS). In this review, we summarize biomarkers in sJIA and CAPS and draw upon the various similarities and differences between the two families of diseases. The main difference between sJIA and CAPS biomarkers are genetic markers with CAPS being a family of monogenic diseases with mutations in NLRP3. There have been a small number of publications describing cellular biomarkers in sJIA with no such studies described for CAPS. Many of the protein markers characteristic of sJIA are also seen to characterize CAPS. The gene expression data in both sJIA and CAPS show a strong upregulation of innate immunity pathways. In addition, we describe a strong similarity between sJIA and CAPS at the gene expression level where several genes that form a part of the erythropoiesis signature are upregulated in both sJIA and CAPS. PMID:25050926

Methotrexate treatment may prevent uveitis onset in patients with juvenile idiopathic arthritis: experiences and subgroup analysis in a cohort with frequent methotrexate use.

PubMed

Kostik, Mikhail M; Gaidar, Ekaterina V; Hynnes, Alla Y; Dubko, Margarita F; Masalova, Vera V; Snegireva, Ludmil S; Chikova, Irina A; Isupova, Eugenia A; Nikitina, Tatiana N; Serogodskaya, Elena D; Kalashnikova, Olga V; Ravelli, Angelo; Chasnyk, Vyacheslav G

2016-01-01

To re-evaluate the ability of methotrexate (MTX) to prevent the onset of uveitis in Russian children with juvenile idiopathic arthritis (JIA). The clinical charts for all consecutive patients who received a stable management for at least 2 years with or without MTX were reviewed. Patients who were given systemic medications other than MTX (except NSAID) and patients with systemic arthritis, rheumatoid factor-positive arthritis, or enthesitis-related arthritis were excluded. Each patient was examined after at least a 2-year follow-up period after the first visit to establish whether uveitis had occurred. A total of 281 patients with a median disease duration of 3.8 years were included. 191 patients (68%) were treated with MTX. During the observation period, 64 patients (22.8%) developed uveitis, a median of 1.6 year after disease onset. The frequency of uveitis was lower in MTX-treated than in MTX-untreated patients (11.5% vs. 46.7%, respectively, OR=6.7 (95%CI:3.7-12.3), p=0.0000001). Survival analysis confirmed that patients treated with MTX had a lower probability of developing uveitis (HR=4.35, p=0.000001). In subgroup analysis it was shown that MTX was more preventive in boys than in girls, and in patients with JIA onset age of over 5 years compared to those with disease onset less than 5 years. The data of survival analysis of MTX prevention has shown that benefits do not depend on the number of active joints and ANA status. MTX therapy may prevent the onset of uveitis in children with JIA. Further randomised controlled trials are required to confirm our results.

Management of juvenile idiopathic arthritis: hitting the target.

PubMed

Hinze, Claas; Gohar, Faekah; Foell, Dirk

2015-05-01

The treatment of juvenile idiopathic arthritis (JIA) is evolving. The growing number of effective drugs has led to successful treatment and prevention of long-term sequelae in most patients. Although patients with JIA frequently achieve lasting clinical remission, sustained remission off medication is still elusive for most. Treatment approaches vary substantially among paediatric rheumatologists owing to the inherent heterogeneity of JIA and, until recently, to the lack of accepted and well-evidenced guidelines. Furthermore, many pertinent questions related to patient management remain unanswered, in particular regarding treatment targets, and selection, intensity and sequence of initiation or withdrawal of therapy. Existing JIA guidelines and recommendations do not specify treat-to-target or tight control strategies, in contrast to adult rheumatology in which these approaches have been successful. The concepts of window of opportunity (early treatment to improve long-term outcomes) and immunological remission (abrogation of subclinical disease activity) are also fundamental when defining treatment methodologies. This Review explores the application of these concepts to JIA and their possible contribution to the development of future clinical guidelines or consensus treatment protocols. The article also discusses how diverse forms of standardized, guideline-led care and personalized treatment can be combined into a targeted, patient-centred approach to optimize management strategies for patients with JIA.

Course, Outcome and Complications in Children with Systemic Onset Juvenile Idiopathic Arthritis.

PubMed

Dewoolkar, Mansi; Cimaz, Rolando; Chickermane, Pranav Raman; Khubchandani, Raju P

2017-04-01

To assess the course, outcome and complications in a mono-centric cohort of 53 patients with systemic onset juvenile idiopathic arthritis (s-JIA). In an observational study, 53 consecutive patients diagnosed with s-JIA on or before October 2009 were enrolled and followed up between October 2009 and September 2012. At each 6-12 weekly visit, clinical examination, laboratory investigations and details of on-going treatment were recorded. Disease course was classified as monocyclic, intermittent and persistent. At last visit, outcome was studied with respect to remission (Wallace criteria) and Steinbrocker functional classification. Juvenile Arthritis Damage Index (JADI) was measured on a subset. In 53 patients analysed, the mean follow-up period was 5.5 ± 1.85 y, with a cumulative follow-up period of 291.5 patient-years. The mean age at diagnosis was 6.3 ± 3.4 y. Thirty-three patients suffered from disease and/or drug related complications. Infections were observed in 16 (30%) and macrophage activation syndrome in 5 (9.4%). Nine (17%) had a monocyclic course, 31 (58.5%) had an intermittent course and 13 (24.5%), a persistent course. At last visit, 9/9 patients of the monocyclic group, 17/31 in the intermittent group and 3/13 in the persistent group were in remission. At the end of the study, 96.2% of the index patients were Steinbrocker functional class I and II with the monocyclic group having the best functional outcome. JADI was performed on 20/53 patients. Nine had significant articular damage. The range of Juvenile arthritis damage index-articular (JADI-A) was 0-25/72 (median-6) and of Juvenile arthritis damage index-extra articular (JADI-EA) was 0-4/17 (median-1). The outcome of patients with s-JIA in a resource limited setting where early diagnosis, multidisciplinary care and availability of biologics are hurdles, is further altered by complications related to longstanding disease and over use of steroids.

A survey of foot problems in juvenile idiopathic arthritis.

PubMed

Hendry, G; Gardner-Medwin, J; Watt, G F; Woodburn, J

2008-12-01

Evidence suggests that foot problems are common in juvenile idiopathic arthritis (JIA), with prevalence estimates over 90%. The aim of this survey was to describe foot-related impairment and disability associated with JIA and foot-care provision in patients managed under modern treatment paradigms, including disease-modifying anti-rheumatic drugs (DMARDs) and biologic therapies. The Juvenile Arthritis Foot Disability Index (JAFI), Child Health Assessment Questionnaire (CHAQ), and pain visual analogue scale (VAS) were recorded in 30 consecutive established JIA patients attending routine outpatient clinics. Foot deformity score, active/limited joint counts, walking speed, double-support time (s) (DS) and step length symmetry index % (SI) were also measured. Foot-care provision in the preceding 12 months was determined from medical records. Sixty-three per cent of children reported some foot impairment, with a median (range) JAFI subscale score of 1 (0-3); 53% reported foot-related activity limitation, with a JAFI subscale score of 1 (0-4); and 60% reported participation restriction, with a JAFI subscale score of 1 (0-3). Other reported variables were CHAQ 0.38 (0-2), VAS pain 22 (0-79), foot deformity 6 (0-20), active joints 0 (0-7), limited joints 0 (0-31), walking speed 1.09 m/s (0.84-1.38 m/s), DS 0.22 s (0.08-0.26 s) and SI +/-4.0% (+/-0.2-+/-31.0%). A total of 23/30 medical records were reviewed and 15/23 children had received DMARDS, 8/23 biologic agents and 20/23 multiple intra-articular corticosteroid injections. Ten children received specialist podiatry care comprising footwear advice, orthotic therapy and silicone digital splints together with intrinsic muscle strengthening exercises. Despite frequent use of DMARD/biologic therapy and specialist podiatry-led foot care, foot-related impairment and disability persists in some children with JIA.

A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis.

PubMed

King, Talmadge E; Bradford, Williamson Z; Castro-Bernardini, Socorro; Fagan, Elizabeth A; Glaspole, Ian; Glassberg, Marilyn K; Gorina, Eduard; Hopkins, Peter M; Kardatzke, David; Lancaster, Lisa; Lederer, David J; Nathan, Steven D; Pereira, Carlos A; Sahn, Steven A; Sussman, Robert; Swigris, Jeffrey J; Noble, Paul W

2014-05-29

In two of three phase 3 trials, pirfenidone, an oral antifibrotic therapy, reduced disease progression, as measured by the decline in forced vital capacity (FVC) or vital capacity, in patients with idiopathic pulmonary fibrosis; in the third trial, this end point was not achieved. We sought to confirm the beneficial effect of pirfenidone on disease progression in such patients. In this phase 3 study, we randomly assigned 555 patients with idiopathic pulmonary fibrosis to receive either oral pirfenidone (2403 mg per day) or placebo for 52 weeks. The primary end point was the change in FVC or death at week 52. Secondary end points were the 6-minute walk distance, progression-free survival, dyspnea, and death from any cause or from idiopathic pulmonary fibrosis. In the pirfenidone group, as compared with the placebo group, there was a relative reduction of 47.9% in the proportion of patients who had an absolute decline of 10 percentage points or more in the percentage of the predicted FVC or who died; there was also a relative increase of 132.5% in the proportion of patients with no decline in FVC (P<0.001). Pirfenidone reduced the decline in the 6-minute walk distance (P=0.04) and improved progression-free survival (P<0.001). There was no significant between-group difference in dyspnea scores (P=0.16) or in rates of death from any cause (P=0.10) or from idiopathic pulmonary fibrosis (P=0.23). However, in a prespecified pooled analysis incorporating results from two previous phase 3 trials, the between-group difference favoring pirfenidone was significant for death from any cause (P=0.01) and from idiopathic pulmonary fibrosis (P=0.006). Gastrointestinal and skin-related adverse events were more common in the pirfenidone group than in the placebo group but rarely led to treatment discontinuation. Pirfenidone, as compared with placebo, reduced disease progression, as reflected by lung function, exercise tolerance, and progression-free survival, in patients with

Abatacept in the treatment of severe, longstanding, and refractory uveitis associated with juvenile idiopathic arthritis.

PubMed

Tappeiner, Christoph; Miserocchi, Elisabetta; Bodaghi, Bahram; Kotaniemi, Kaisu; Mackensen, Friederike; Gerloni, Valeria; Quartier, Pierre; Lutz, Thomas; Heiligenhaus, Arnd

2015-04-01

Abatacept (ABA), a selective T cell costimulation modulator that binds to CD80 and CD86 on antigen-presenting cells, was investigated for its antiinflammatory effect in treating severe chronic uveitis associated with juvenile idiopathic arthritis (JIA). Our retrospective study was conducted by members of the Multinational Interdisciplinary Working Group for Uveitis in Childhood (MIWGUC). Patients with JIA who are receiving ABA treatment for active uveitis were included. In all patients, uveitis had been refractory to previous topical and systemic corticosteroids, immunosuppressives, and at least 1 tumor necrosis factor-α inhibitor. A standardized protocol was used to document uveitis (MIWGUC) and arthritis. Baseline visit and visits at 3, 6, 9, and 12 months before and after ABA start were evaluated. Primary outcome measure was defined as achievement of uveitis inactivity; secondary outcome measures were tapering of corticosteroid and/or immunosuppressive treatment, and occurrence of complications. In all, 21 patients (16 female) with active uveitis (n = 21) and arthritis (n = 18) were included (mean age 11.8 ± 3.6 yrs). In 7 of 18 patients with active arthritis at baseline, inactivity was achieved following ABA treatment. Uveitis inactivity was achieved in 11 patients, but recurred later in 8 of them, and remained active in another 10 cases. Systemic corticosteroids or immunosuppression were tapered in 3 patients, but uveitis recurred in all of them during further followup. Ocular complications secondary to uveitis were present in 17 patients at baseline, while 3 patients developed new ocular complications during followup. A sustained response to ABA was uncommon in patients with severe and refractory uveitis.

American College of Rheumatology provisional criteria for defining clinical inactive disease in select categories of juvenile idiopathic arthritis.

PubMed

Wallace, Carol A; Giannini, Edward H; Huang, Bin; Itert, Lukasz; Ruperto, Nicolino

2011-07-01

To prospectively validate the preliminary criteria for clinical inactive disease (CID) in patients with select categories of juvenile idiopathic arthritis (JIA). We used the process for development of classification and response criteria recommended by the American College of Rheumatology Quality of Care Committee. Patient-visit profiles were extracted from the phase III randomized controlled trial of infliximab in polyarticular-course JIA (i.e., patients considered to resemble those with select categories of JIA) and sent to an international group of expert physician raters. Using the physician ratings as the gold standard, the sensitivity and specificity were calculated using the preliminary criteria. Modifications to the criteria were made, and these were sent to a larger group of pediatric rheumatologists to determine quantitative, face, and content validity. Variables weighted heaviest by physicians when making their judgment were the number of joints with active arthritis, erythrocyte sedimentation rate (ESR), physician's global assessment, and duration of morning stiffness. Three modifications were made: the definition of uveitis, the definition of abnormal ESR, and the addition of morning stiffness. These changes did not alter the accuracy of the preliminary set. The modified criteria, termed the "criteria for CID in select categories of JIA," have excellent feasibility and face, content, criterion, and discriminant validity to detect CID in select categories of JIA. The small changes made to the preliminary criteria set did not alter the area under the receiver operating characteristic curve (0.954) or accuracy (91%), but have increased face and content validity. Copyright © 2011 by the American College of Rheumatology.

Ghrelin levels in patients with juvenile idiopathic arthritis: relation to anti-tumor necrosis factor treatment and disease activity.

PubMed

Karagiozoglou-Lampoudi, Thomais; Trachana, Maria; Agakidis, Charalampos; Pratsidou-Gertsi, Polyxeni; Taparkou, Anna; Lampoudi, Sotiria; Kanakoudi-Tsakalidou, Florentia

2011-10-01

Studies in adults with rheumatoid arthritis reported low serum ghrelin that increased following anti-tumor necrosis factor (TNF) infusion. Data on juvenile idiopathic arthritis (JIA) are lacking. The aim of this pilot study was to explore serum ghrelin levels in patients with JIA and the possible association with anti-TNF treatment, disease activity, and nutritional status. Fifty-two patients with JIA (14/52 on anti-TNF treatment) were studied. Juvenile idiopathic arthritis was inactive in 3 of 14 anti-TNF-treated patients and in 11 of 38 non-anti-TNF-treated patients. The nutritional status, energy intake/requirements, appetite, and fasting serum ghrelin levels were assessed. Ghrelin control values were obtained from 50 individuals with minor illness matched for age, sex, and body mass index. Ghrelin levels in patients with JIA were significantly lower than in controls (P < .001, confidence interval [CI] = -101 to -331). Analysis according to anti-TNF treatment and disease activity showed that ghrelin levels were comparable to control values only in 3 patients with anti-TNF-induced remission. Ghrelin in non-anti-TNF-treated patients in remission was low. Multiple regression analysis showed that disease activity (P = .002, CI = -84.16 to -20.01) and anti-TNF treatment (P = .003, CI = -82.51 to -18.33) were significant independent predictors of ghrelin after adjusting for other potential confounders. Ghrelin did not correlate with nutritional status, energy balance, and appetite. Serum ghrelin is low in patients with JIA and is restored to values similar to those in controls following anti-TNF-induced remission. Our study provides evidence that TNF blockade is independently associated with serum ghrelin, which possibly contributes to anti-TNF-induced remission. These preliminary results could form the basis for future research. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of pirfenidone on mortality: pooled analyses and meta-analyses of clinical trials in idiopathic pulmonary fibrosis.

PubMed

Nathan, Steven D; Albera, Carlo; Bradford, Williamson Z; Costabel, Ulrich; Glaspole, Ian; Glassberg, Marilyn K; Kardatzke, David R; Daigl, Monica; Kirchgaessler, Klaus-Uwe; Lancaster, Lisa H; Lederer, David J; Pereira, Carlos A; Swigris, Jeffrey J; Valeyre, Dominique; Noble, Paul W

2017-01-01

In clinical trials of idiopathic pulmonary fibrosis, rates of all-cause mortality are low. Thus prospective mortality trials are logistically very challenging, justifying the use of pooled analyses or meta-analyses. We did pooled analyses and meta-analyses of clinical trials of pirfenidone versus placebo to determine the effect of pirfenidone on mortality outcomes over 120 weeks. We did a pooled analysis of the combined patient populations of the three global randomised phase 3 trials of pirfenidone versus placebo-Clinical Studies Assessing Pirfenidone in Idiopathic Pulmonary Fibrosis: Research of Efficacy and Safety Outcomes (CAPACITY 004 and 006; trial durations 72-120 weeks) and Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis (ASCEND 016; 52 weeks)-for all-cause mortality, treatment-emergent all-cause mortality, idiopathic-pulmonary-fibrosis-related mortality, and treatment-emergent idiopathic-pulmonary-fibrosis-related mortality at weeks 52, 72, and 120. We also did meta-analyses of these data and data from two Japanese trials of pirfenidone versus placebo-Shionogi Phase 2 (SP2) and Shionogi Phase 3 (SP3; trial durations 36-52 weeks). At week 52, the relative risk of death for all four mortality outcomes was significantly lower in the pirfenidone group than in the placebo group in the pooled population (all-cause mortality hazard ratio [HR] 0·52 [95% CI 0·31-0·87; p=0·0107]; treatment-emergent all-cause mortality 0·45 [0·24-0·83; 0·0094]; idiopathic-pulmonary-fibrosis-related mortality 0·35 [0·17-0·72; 0·0029]; treatment-emergent idiopathic-pulmonary-fibrosis-related mortality 0·32 [0·14-0·76; 0·0061]). Consistent with the pooled analysis, meta-analyses for all-cause mortality at week 52 also showed a clinically relevant and significant risk reduction in the pirfenidone group compared with the placebo group. Over 120 weeks, we noted significant differences in the pooled analysis favouring pirfenidone

Seroprevalence of parvovirus B19 IgG in children affected by juvenile idiopathic arthritis

PubMed Central

Weissbrich, Benedikt; Süß-Fröhlich, Yvonne; Girschick, Hermann J

2007-01-01

Parvovirus (PV) B19 is the causative agent of the childhood disease erythema infectiosum. An association of PV B19 with chronic arthropathies, sometimes resembling rheumatoid arthritis or juvenile idiopathic arthritis (JIA), has repeatedly been described. Other studies, however, have failed to identify any such relationship. In order to study further whether there is a link between PV B19 and JIA, we determined the prevalence of PV B19 specific IgG antibodies in serum samples from children with rheumatoid diseases and compared it with the prevalence in unaffected children We reasoned that if there is an association between PV B19 and JIA, then the prevalence of PV B19 IgG in the children with JIA should be higher than in the control group. PV B19 IgG status was tested in 406 children with JIA and related diseases, and in 146 children constituting a control group. The percentage of PV B19 IgG positive children was not significantly elevated in the disease subgroups compared with age-matched control groups. In conclusion, our findings do not support the hypothesis that human parvovirus B19 is involved in the pathogenesis of JIA. PMID:17760961

Ultrasound in Arthritis.

PubMed

Sudoł-Szopińska, Iwona; Schueller-Weidekamm, Claudia; Plagou, Athena; Teh, James

2017-09-01

Ultrasound is currently performed in everyday rheumatologic practice. It is used for early diagnosis, to monitor treatment results, and to diagnose remission. The spectrum of pathologies seen in arthritis with ultrasound includes early inflammatory features and associated complications. This article discusses the spectrum of ultrasound features of arthritides seen in rheumatoid arthritis and other connective tissue diseases in adults, such as Sjögren syndrome, lupus erythematosus, dermatomyositis, polymyositis, and juvenile idiopathic arthritis. Ultrasound findings in spondyloarthritis, osteoarthritis, and crystal-induced diseases are presented. Ultrasound-guided interventions in patients with arthritis are listed, and the advantages and disadvantages of ultrasound are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

The Idiopathic Intracranial Hypertension Treatment Trial

PubMed Central

Wall, Michael; Kupersmith, Mark J.; Kieburtz, Karl D.; Corbett, James J.; Feldon, Steven E.; Friedman, Deborah I.; Katz, David M.; Keltner, John L.; Schron, Eleanor B.; McDermott, Michael P.

2015-01-01

IMPORTANCE To our knowledge, there are no large prospective cohorts of untreated patients with idiopathic intracranial hypertension (IIH) to characterize the disease. OBJECTIVE To report the baseline clinical and laboratory features of patients enrolled in the Idiopathic Intracranial Hypertension Treatment Trial. DESIGN, SETTING, AND PARTICIPANTS We collected data at baseline from questionnaires, examinations, automated perimetry, and fundus photography grading. Patients (n = 165) were enrolled from March 17, 2010, to November 27, 2012, at 38 academic and private practice sites in North America. All participants met the modified Dandy criteria for IIH and had a perimetric mean deviation between −2 dB and −7 dB. All but 4 participants were women. MAIN OUTCOMES AND MEASURES Baseline and laboratory characteristics. RESULTS The mean (SD) age of our patients was 29.0 (7.4) years and 4 (2.4%) were men. The average (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 39.9 (8.3). Headache was the most common symptom (84%). Transient visual obscurations occurred in 68% of patients, back pain in 53%, and pulse synchronous tinnitus in 52%. Only 32% reported visual loss. The average (SD) perimetric mean deviation in the worst eye was −3.5 (1.1) dB, (range, −2.0 to −6.4 dB) and in the best eye was −2.3 (1.1) dB (range, −5.2 to 0.8 dB). A partial arcuate visual field defect with an enlarged blind spot was the most common perimetric finding. Visual acuity was 85 letters or better (20/20) in 71% of the worst eyes and 77% of the best eyes. Quality of life measures, including the National Eye Institute Visual Function Questionnaire–25 and the Short Form–36 physical and mental health summary scales, were lower compared with population norms. CONCLUSIONS AND RELEVANCE The Idiopathic Intracranial Hypertension Treatment Trial represents the largest prospectively analyzed cohort of untreated patients with IIH. Our data show

Childhood Arthritis and Rheumatology Research Alliance consensus treatment plans for new-onset polyarticular juvenile idiopathic arthritis.

PubMed

Ringold, Sarah; Weiss, Pamela F; Colbert, Robert A; DeWitt, Esi Morgan; Lee, Tzielan; Onel, Karen; Prahalad, Sampath; Schneider, Rayfel; Shenoi, Susan; Vehe, Richard K; Kimura, Yukiko

2014-07-01

There is no standardized approach to the initial treatment of polyarticular juvenile idiopathic arthritis (JIA) among pediatric rheumatologists. Understanding the comparative effectiveness of the diverse therapeutic options available will result in better health outcomes for polyarticular JIA. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans (CTPs) for use in clinical practice to facilitate such studies. A case-based survey was administered to CARRA members to identify the common treatment approaches for new-onset polyarticular JIA. Two face-to-face consensus conferences employed modified nominal group technique to identify treatment strategies, operational case definition, end points, and data elements to be collected. A core workgroup reviewed the relevant literature, refined plans, and developed medication dosing and monitoring recommendations. The initial case-based survey identified significant variability among treatment approaches for new-onset polyarticular JIA. We developed 3 CTPs based on treatment strategies for the first 12 months of therapy, as well as case definitions and clinical and laboratory monitoring schedules. The CTPs include a step-up plan (nonbiologic disease-modifying antirheumatic drug [DMARD] followed by a biologic DMARD), an early combination plan (nonbiologic and biologic DMARD combined within a month of treatment initiation), and a biologic only plan. This approach was approved by 96% of the CARRA JIA Research Committee members attending the 2013 CARRA face-to-face meeting. Three standardized CTPs were developed for new-onset polyarticular JIA. Coupled with data collection at defined intervals, use of these CTPs will enable the study of their comparative effectiveness in an observational setting to optimize initial management of polyarticular JIA. Copyright © 2014 by the American College of Rheumatology.

Pilot study comparing the Childhood Arthritis & Rheumatology Research Alliance (CARRA) systemic Juvenile Idiopathic Arthritis Consensus Treatment Plans.

PubMed

Kimura, Yukiko; Grevich, Sriharsha; Beukelman, Timothy; Morgan, Esi; Nigrovic, Peter A; Mieszkalski, Kelly; Graham, T Brent; Ibarra, Maria; Ilowite, Norman; Klein-Gitelman, Marisa; Onel, Karen; Prahalad, Sampath; Punaro, Marilynn; Ringold, Sarah; Toib, Dana; Van Mater, Heather; Weiss, Jennifer E; Weiss, Pamela F; Schanberg, Laura E

2017-04-11

To assess the feasibility of studying the comparative effectiveness of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) consensus treatment plans (CTPs) for systemic Juvenile Idiopathic Arthritis (JIA) using an observational registry. Untreated systemic JIA patients enrolled in the CARRA Registry were begun on one of 4 CTPs chosen by the treating physician and patient/family (glucocorticoid [GC] alone; methotrexate [MTX] ± GC; IL1 inhibitor [IL1i] ± GC; IL6 inhibitor [IL6i] ± GC). The primary outcome of clinical inactive disease (CID) without current GC use was assessed at 9 months. clinicaltrials.gov NCT01697254; first registered 9/28/12 (retrospectively enrolled). Thirty patients were enrolled at 13 sites; eight patients were started on a non-biologic CTP (2 GC, 6 MTX) and 22 patients on a biologic CTP (12 IL1i, 10 IL6i) at disease onset. Demographic and disease features were similar between CTP groups. CTP choice appeared to segregate by site preference. CID off GC was achieved by 37% (11 of 30) including 11/22 (50%) starting a biologic CTP compared to 0/8 starting a non-biologic CTP (p = 0.014). There were four serious adverse events: two infections, one appendicitis and one macrophage activation syndrome. The CARRA systemic JIA CTP pilot study demonstrated successful implementation of CTPs using the CARRA registry infrastructure. Having demonstrated feasibility, a larger study using CTP response to better determine the relative effectiveness of treatments for new-onset systemic JIA is now underway.

Pulmonary Hypertension and Other Potentially Fatal Pulmonary Complications in Systemic Juvenile Idiopathic Arthritis

PubMed Central

Kimura, Yukiko; Weiss, Jennifer E.; Haroldson, Kathryn L.; Lee, Tzielan; Punaro, Marilynn; Oliveira, Sheila; Rabinovich, Egla; Riebschleger, Meredith; Antón, Jordi; Blier, Peter R.; Gerloni, Valeria; Hazen, Melissa M; Kessler, Elizabeth; Onel, Karen; Passo, Murray H; Rennebohm, Robert M; Wallace, Carol A; Woo, Patricia; Wulffraat, Nico

2015-01-01

Objectives Systemic Juvenile Idiopathic Arthritis (sJIA) is characterized by fevers, rash and arthritis, for which IL1 and IL6 inhibitors appear effective. Pulmonary artery hypertension (PAH), interstitial lung disease (ILD) and alveolar proteinosis (AP) have been recently reported in sJIA patients with increased frequency. Our aim was to characterize and compare these cases to a larger cohort of sJIA patients. Methods sJIA patients who developed PAH, ILD and/or AP were identified through an electronic listserv, and their demographic, sJIA and pulmonary disease characteristics, and medication exposure information were collected. These features were compared to a cohort of sJIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Results Patients (N=25) were significantly (p<0.05) more likely than the CARRA registry cohort (N=389) to be female, have more systemic features, and to have been exposed to an IL-1 inhibitor, tocilizumab, infliximab, corticosteroids, intravenous immunoglobulin, cyclosporine and cyclophosphamide. Eighty% were diagnosed after 2004. Twenty (80%) patients had MAS during their disease course and 15 (60%) had MAS at pulmonary diagnosis. Sixteen patients had PAH, 5 AP and 7 ILD. Seventeen (68%) patients were taking or recently (≤1 month) discontinued a biologic agent at pulmonary symptom onset; 12 (48%) were taking anti-IL1 therapy (primarily anakinra). Seventeen (68%) patients died at a mean of 8.8 months from pulmonary diagnosis. Conclusions PAH, AP and ILD are under-recognized complications of sJIA which are frequently fatal. These may be the result of severe uncontrolled systemic disease activity, and may be influenced by medication exposure. PMID:23139240

Allogeneic hematopoietic stem cell transplantation for severe, refractory juvenile idiopathic arthritis

PubMed Central

Ladomenou, Fani; Carpenter, Ben; Chandra, Sharat; Sedlacek, Petr; Formankova, Renata; Grandage, Vicky; Friswell, Mark; Cant, Andrew J.; Nademi, Zohreh; Slatter, Mary A.; Gennery, Andrew R.; Hambleton, Sophie; Flood, Terence J.; Lucchini, Giovanna; Chiesa, Robert; Rao, Kanchan; Amrolia, Persis J.; Brogan, Paul; Wedderburn, Lucy R.; Glanville, Julie M.; Hough, Rachael; Marsh, Rebecca; Abinun, Mario; Veys, Paul

2018-01-01

Patients with juvenile idiopathic arthritis (JIA) can experience a severe disease course, with progressive destructive polyarthritis refractory to conventional therapy with disease-modifying antirheumatic drugs including biologics, as well as life-threatening complications including macrophage activation syndrome (MAS). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative immunomodulatory strategy for patients with such refractory disease. We treated 16 patients in 5 transplant centers between 2007 and 2016: 11 children with systemic JIA and 5 with rheumatoid factor–negative polyarticular JIA; all were either refractory to standard therapy, had developed secondary hemophagocytic lymphohistiocytosis/MAS poorly responsive to treatment, or had failed autologous HSCT. All children received reduced toxicity fludarabine-based conditioning regimens and serotherapy with alemtuzumab. Fourteen of 16 patients are alive with a median follow-up of 29 months (range, 2.8-96 months). All patients had hematological recovery. Three patients had grade II-IV acute graft-versus-host disease. The incidence of viral infections after HSCT was high, likely due to the use of alemtuzumab in already heavily immunosuppressed patients. All patients had significant improvement of arthritis, resolution of MAS, and improved quality of life early following allo-HSCT; most importantly, 11 children achieved complete drug-free remission at the last follow-up. Allo-HSCT using alemtuzumab and reduced toxicity conditioning is a promising therapeutic option for patients with JIA refractory to conventional therapy and/or complicated by MAS. Long-term follow-up is required to ascertain whether disease control following HSCT continues indefinitely. PMID:29618462

Controversies in juvenile idiopathic arthritis-associated uveitis.

PubMed

Zierhut, Manfred; Heiligenhaus, Arnd; deBoer, Joke; Cunningham, Emmett T; Tugal-Tutkun, Ilknur

2013-06-01

Abstract Juvenile idiopathic arthritis-associated uveitis (JIAU) accounts for a sizable proportion of uveitis cases in children and is an important cause of ocular morbidity in uveitis patients in this age group. The authors present the results of a survey conducted to obtain a better understanding of the current views and practices of ophthalmologists involved in the care of children with JIAU. A detailed questionnaire consisting of 54 questions addressing epidemiology, diagnosis, and therapy of JIAU was distributed to 67 uveitis specialists. The responses from 37 completed questionnaires were tabulated for this report. While the experts often agreed on aspects of the epidemiologic and clinical features of JIAU and its complications, considerable diversity of responses was noted-particularly with regard to practice patterns. Regarding diagnostics and disease monitoring, all experts favored ANA testing, whereas two-thirds also suggested HLA-B27 typing. Laser flare photometry was available to and routinely used by almost one-third of the experts. Optical coherence tomography (OCT) was used by more than half. The survey revealed an overall consensus on therapeutic strategies, including the use of both conventional immunosuppressive and biologic agents. Methotrexate was the initial choice for immunosuppression by most respondents. Most would add an anti-TNF-alpha agent following failure of traditional immunosuppressive therapy, and adalimumab was favored by almost half of the experts. Questions addressing the management of individual situations, such as the treatment of macular edema and perioperative management, revealed considerable differences in therapeutic approaches. The results of this survey support the development of international guidelines for the management of JIAU.

Cross-cultural adaptation, reliability, and validity of the Turkish version of PedsQL 3.0 Arthritis Module: a quality-of-life measure for patients with juvenile idiopathic arthritis in Turkey.

PubMed

Tarakci, E; Baydogan, S N; Kasapcopur, O; Dirican, A

2013-04-01

The aim of this study was to describe the cultural adaptation, validity, and reliability of a Turkish version of the pediatric quality-of-life inventory (PedsQL) 3.0 Arthritis Module in a population with juvenile idiopathic arthritis (JIA). A total of 169 patients with JIA and their parents were enrolled in the study. The Turkish version of the childhood health assessment questionnaire (CHAQ) was used to evaluate the validity of related domains in the PedsQL 3.0 Arthritis Module. Both the PedsQL 3.0 Arthritis Module and CHAQ were filled out by children over 8 years of age and by the parents of children 2-7 years of age. Internal reliability was poor to excellent (Cronbach's alpha coefficients 0.56-0.84 for self-reporting and 0.63-0.82 for parent reporting), and interobserver reliability varied from good to excellent (intraclass correlation coefficient (ICC) 0.79-0.91 for self-reporting and 0.80-0.88 for parent reporting) for the total scores of the PedsQL 3.0 Arthritis Module. Parent-child concordance for all scores was moderate to excellent (ICC 0.42-0.92). The PedsQL 3.0 Arthritis Module and CHAQ were highly positively correlated, with coefficients from 0.21 to 0.76, indicating concurrent validity. We demonstrated the reliability and validity of quality-of-life measurement using the Turkish version of the PedsQL 3.0 Arthritis Module in our sociocultural context. The PedsQL 3.0 Arthritis Module can be utilized as a tool for the evaluation of quality of life in patients with JIA aged 2-18 years.

Do all patients with idiopathic pulmonary fibrosis warrant a trial of therapeutic intervention? A pro-con perspective.

PubMed

Moodley, Yuben; Corte, Tamera; Richeldi, Luca; King, Talmadge E

2015-04-01

Idiopathic pulmonary fibrosis (IPF) is an incurable condition that is characterized by progressive pulmonary fibrosis, architectural distortion of the lung and loss of gas exchange units. Until recently, there was no effective treatment for this condition. However, there were two landmark trials published earlier this year, which have changed the management of this condition. Pirfenidone (Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis trial) and nintedanib (Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis-1 and -2 trials) have both demonstrated positive outcomes in patients with IPF. In this perspective, we critically discuss the role of these agents in IPF and in the broader pulmonary fibrosis population. © 2015 Asian Pacific Society of Respirology.

Erythrocyte sedimentation rate as baseline predictor for the development of uveitis in children with juvenile idiopathic arthritis.

PubMed

Haasnoot, Arenda J W; van Tent-Hoeve, Maretta; Wulffraat, Nico M; Schalij-Delfos, Nicoline E; Los, Leonoor I; Armbrust, Wineke; Zuithoff, Nicolaas P A; de Boer, Joke H

2015-02-01

To analyze inflammatory parameters as possible predictors for the development of uveitis in juvenile idiopathic arthritis (JIA) patients. Further, to analyze the predictive value of demographic and clinical factors at the onset of arthritis. Retrospective cohort study. In 358 children with oligoarthritis and rheumatoid factor-negative polyarthritis, erythrocyte sedimentation rate (ESR), C-reactive protein, leukocyte count, presence of antinuclear antibodies (ANA), presence of human leukocyte antigen (HLA-)B27, age of onset of JIA, and sex were analyzed for their predictive value for the onset of uveitis. One hundred forty-seven patients (41%) were diagnosed with chronic anterior uveitis. Young age of onset, presence of ANA, and elevated ESR appeared to be predictive factors according to univariate analyses (P = .029, P = .007, and P = 5E(-4), respectively). According to multivariate analysis, young age of onset and elevated ESR appeared to be predictive after adjusting for the other relevant factors (P = .004 and P = .001, respectively). A prediction model was developed. Elevated ESR appears to be a predictor for the occurrence of uveitis in patients with JIA. Since ESR is already routinely tested in patients with recently diagnosed arthritis, its use as a biomarker can easily be implemented in daily practice. Copyright © 2015 Elsevier Inc. All rights reserved.

Juvenile idiopathic arthritis and athletic participation: are we adequately preparing for sports integration?

PubMed

Taxter, Alysha; Foss, Kim Barber; Melson, Paula; Ford, Kevin R; Shaffer, Michael; Myer, Gregory D

2012-09-01

Children with juvenile idiopathic arthritis (JIA) now have well-controlled disease due to improved therapies and management strategies. Children with JIA are more active than in the past and often participate in dynamic, high-loading sports. Standard measures of disease control include examination findings, laboratory values, and patient-directed surveys. However, these standards do not address the subtle deficits in biomechanics and neuromuscular control, which could place affected joints at higher risk for injury. Currently, there are limited evidence-based guidelines to structure conditioning recommendations as to the fitness and mechanics needed to provide safe integration into sports in this population; therefore, tools that objectively measure function with high accuracy and precision may be warranted. Previous work using 3-dimensional motion analysis demonstrated usefulness in guiding physical therapy treatment to correct these deficits. The use of a multidisciplinary team, including physical therapy, rheumatology, and sports medicine, is crucial for preparing these children to return to play. We suggest that the child transition into a sport preparatory-conditioning program to address any underlying deficits. A pediatric exercise specialist who is sensitive to the needs of this population can work with a physical therapist to then appropriately integrate the child safely into sport. Encouraging an active lifestyle is vital to the management of JIA and does not worsen the symptoms associated with childhood arthritis.

Methotrexate is an effective treatment for chronic uveitis associated with juvenile idiopathic arthritis.

PubMed

Foeldvari, Ivan; Wierk, Angela

2005-02-01

To assess the effectiveness of methotrexate (MTX) in the treatment of juvenile idiopathic arthritis (JIA) associated uveitis, which is still one of the most common causes of visual impairment. A retrospective chart review of patients with the diagnosis of uveitis associated with JIA between July 1, 2002, and December 31, 2002. Four hundred sixty-seven patients with JIA were followed. Thirty-eight had uveitis: 31 associated with oligoarticular JIA and 7 with psoriatic JIA. Twenty-five of the 38 patients received MTX; in 23 patients uveitis was the indication for MTX therapy. In the MTX treated group 46/50 eyes had uveitis, the mean (range) age at onset of uveitis was 7.82 years (1.8-15.8), and the mean age at onset of arthritis was 7.25 years (1.25-15.7). MTX treatment was started an average of 11.4 months (0-72) after the onset of uveitis. The mean MTX dose was 15.6 mg/m2. Remission occurred after 4.25 months (1-12). Mean duration of remission was 10.3 months (3-27). The total duration of MTX therapy was 661 months and patients were in remission for 417/661 months. In 6 patients MTX was discontinued after 12 months of remission. Four patients were still in remission after 7.5 months (1-14). MTX seems to be an effective therapy for JIA associated uveitis.

CXCR6-CXCL16 interaction in the pathogenesis of Juvenile Idiopathic Arthritis.

PubMed

Martini, Giorgia; Cabrelle, Anna; Calabrese, Fiorella; Carraro, Samuela; Scquizzato, Elisa; Teramo, Antonella; Facco, Monica; Zulian, Francesco; Agostini, Carlo

2008-11-01

In order to evaluate the role of CXCR6/CXCL16 in driving lymphocyte migration into inflamed joints of children with oligoarticular Juvenile Idiopathic Arthritis (JIA) we analysed CXCR6 expression and functional capability in lymphocytes from synovial fluid (SF) by flow cytometry, by real-time polymerase chain reaction (RT-PCR) and migration assays. Furthermore, CXCR6 and CXCL16 expression in synovial tissue (ST) was analysed by immunohistochemistry. T cells isolated from SF of patients with JIA expressed CXCR6 which was functionally active as shown by chemotactic assays. The same cells expressed CXCR3 and it exerted a migratory activity in response to CXCL10. CXCL16 and CXCR6 were intensively expressed on the synovium cells, respectively on macrophages, synoviocytes and endothelial cells and on lymphocytes, synoviocytes and endothelial cells. Taken together, these data suggest that CXCR6 and CXCR3 act coordinately with respective ligands and are involved in the pathophysiology of JIA-associated inflammatory processes.

Fever as an Initial Manifestation of Enthesitis-Related Arthritis Subtype of Juvenile Idiopathic Arthritis: Retrospective Study

PubMed Central

Guo, Ruru; Cao, Lanfang; Kong, Xianming; Liu, Xuesong; Xue, Haiyan; Shen, Lijuan; Li, Xiaoli

2015-01-01

Objective We wished to determine the prevalence of fever as one of the first symptoms of the enthesitis-related arthritis (ERA) subtype of juvenile idiopathic arthritis. Also, we wished to ascertain if ERA patients with fever at disease onset differed from those without fever. Methods Consecutive cases of ERA were diagnosed and followed in a retrospective observational study from 1998 to 2013. Information about clinical/laboratory data, medications, magnetic resonance imaging (MRI), and disease activity during the study period was also recorded. Results A total of 146 consecutive ERA patients were assessed. Among them, 52 patients (35.6%) had fever as one of the first symptoms at disease onset. Compared with ERA patients without fever at disease onset, patients with fever had significantly more painful joints (3.5 vs. 2.8), more swollen joints (1.1 vs. 0.8), and more enthesitis (1.0 vs. 0.4) (p<0.05 for all comparisons). Patients with fever had significantly higher mean values of erythrocyte sedimentation rate, C-reactive protein, platelet count, and child health assessment questionnaire (CHAQ) scores (40.8 vs. 26.4 mm/h; 20.7 vs. 9.7 mg/dL; 353.2×109/L vs. 275.6×109/L; 1.0 vs. 0.8, respectively; all p<0.05). During two-year follow-up, CHAQ score, number of flares, as well as the number of patients treated with oral non-steroidal anti-inflammatory drugs, corticosteroids and combination therapy with disease-modifying anti-rheumatic drugs, were significantly higher in ERA patients with fever. Conclusions Fever was a frequent manifestation of ERA. ERA patients with fever had more active disease at disease onset and poorer outcomes than ERA patients without fever. PMID:26030261

Prevalence of overweight in children and adolescents with juvenile idiopathic arthritis.

PubMed

Schenck, S; Niewerth, M; Sengler, C; Trauzeddel, R; Thon, A; Minden, K; Klotsche, J

2015-01-01

To assess the prevalence of overweight in patients with juvenile idiopathic arthritis (JIA) between 2003 and 2012 and to determine correlates of overweight relevant to the change in the overweight rate. Annual overweight prevalence was determined in the National Paediatric Rheumatological Database (NPRD) between 2003 and 2012. The prevalence of overweight in JIA was compared to representative data from Germany in 2005. The median age of JIA patients was 11.5 years and the mean disease duration 4 years. Almost 50% of JIA patients had persistent oligoarthritis, followed by rheumatoid factor (RF)-negative polyarthritis (14%). The overweight prevalence decreased significantly from 14.2% in 2003 to 8.3% in 2012 [odds ratio (OR) 0.92, 95% confidence interval (CI) 0.89-0.95]. Higher levels of physical activity and less frequent treatment with high-dose glucocorticoids (GCs) were associated with decreasing overweight rates. Systemic JIA had the highest decrease in the overweight rate over time. Patients with JIA had an overweight rate comparable to that of children and adolescents in the general population. However, systemic JIA and enthesitis-related arthritis were more likely to be associated with overweight. The use of high-dose GCs, lower functional limitations, and a lower level (or lack) of participation in school sports were significant predictors of overweight in multivariable analyses. The prevalence of overweight in JIA was comparable to the general population and decreased significantly over time. The decrease was associated with higher functional ability and JIA patients should be encouraged to be more physically active. The role of an elevated body mass index (BMI) in the long-term outcome of JIA needs to be addressed in future studies.

Clinical trials in rheumatoid arthritis: a status report from the ClinicalTrials.gov website.

PubMed

Paul, Jisna R; Ranganathan, Prabha

2012-06-01

The aims of this study are to describe the characteristics of clinical trials in rheumatoid arthritis (RA) listed in ClinicalTrials.gov and examine existing trends in study design, funding sources, outcomes, and drugs under investigation. We conducted a survey of ongoing clinical trials in RA registered in the ClinicalTrials.gov website. We used the advanced search option and applied the following inclusion criteria, "rheumatoid arthritis", "open studies", "interventional", and "adults 18 years or older". Of 127 eligible trials, 53.5% of the studies were either phase 3 or 4, and 40.2% were phase 1, 2, and 2/3. Two-thirds of the trials were randomized (70.9%), and over half were, in addition, double-blinded (53.5%) and placebo-controlled (53.5%). Universities were listed as the primary sponsor for 18.9% of the trials and pharmaceutical industry for 73.2%. Majority of the trials were multi-center studies (93%) conducted outside the United States (54.3%). The most frequently used endpoint was drug efficacy (54.3%) followed by drug safety (25.2%). Most industry-funded trials were open for less than 12 months, whereas most university-funded trials were open for more than 24 months (58% each). Biologic therapies were the focus of most trials in the registry (78.5%). Randomized, double-blinded, placebo-controlled, phase 3 and 4 trials form the majority of ongoing clinical trials in RA. The preponderance of industry funding of RA trials and the short duration of such trials are troubling trends which need to be addressed.

Treating juvenile idiopathic arthritis to target: recommendations of an international task force.

PubMed

Ravelli, Angelo; Consolaro, Alessandro; Horneff, Gerd; Laxer, Ronald M; Lovell, Daniel J; Wulffraat, Nico M; Akikusa, Jonathan D; Al-Mayouf, Sulaiman M; Antón, Jordi; Avcin, Tadej; Berard, Roberta A; Beresford, Michael W; Burgos-Vargas, Ruben; Cimaz, Rolando; De Benedetti, Fabrizio; Demirkaya, Erkan; Foell, Dirk; Itoh, Yasuhiko; Lahdenne, Pekka; Morgan, Esi M; Quartier, Pierre; Ruperto, Nicolino; Russo, Ricardo; Saad-Magalhães, Claudia; Sawhney, Sujata; Scott, Christiaan; Shenoi, Susan; Swart, Joost F; Uziel, Yosef; Vastert, Sebastiaan J; Smolen, Josef S

2018-06-01

Recent therapeutic advances in juvenile idiopathic arthritis (JIA) have made remission an achievable goal for most patients. Reaching this target leads to improved outcomes. The objective was to develop recommendations for treating JIA to target. A Steering Committee formulated a set of recommendations based on evidence derived from a systematic literature review. These were subsequently discussed, amended and voted on by an international Task Force of 30 paediatric rheumatologists in a consensus-based, Delphi-like procedure. Although the literature review did not reveal trials that compared a treat-to-target approach with another or no strategy, it provided indirect evidence regarding an optimised approach to therapy that facilitated development of recommendations. The group agreed on six overarching principles and eight recommendations. The main treatment target, which should be based on a shared decision with parents/patients, was defined as remission, with the alternative target of low disease activity. The frequency and timeline of follow-up evaluations to ensure achievement and maintenance of the target depend on JIA category and level of disease activity. Additional recommendations emphasise the importance of ensuring adequate growth and development and avoiding long-term systemic glucocorticoid administration to maintain the target. All items were agreed on by more than 80% of the members of the Task Force. A research agenda was formulated. The Task Force developed recommendations for treating JIA to target, being aware that the evidence is not strong and needs to be expanded by future research. These recommendations can inform various stakeholders about strategies to reach optimal outcomes for JIA. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Intravenous immunoglobulin and idiopathic secondary recurrent miscarriage: a multicentered randomized placebo-controlled trial

PubMed Central

Stephenson, Mary D.; Kutteh, William H.; Purkiss, Susan; Librach, Cliff; Schultz, Patricia; Houlihan, Edwina; Liao, Chuanhong

2010-01-01

BACKGROUND Idiopathic secondary recurrent miscarriage may be associated with an abnormal maternal immune response to subsequent pregnancies. Intravenous immunoglobulin (IVIG) has been studied in randomized controlled trials (RCTs) with conflicting results. Therefore, a definitive trial was proposed. METHODS We conducted an investigator-initiated, multicentered, randomized, double-blinded, placebo-controlled trial comparing IVIG with saline in women with idiopathic secondary recurrent miscarriage, defined as a history of at least one prior ongoing pregnancy followed by three or more consecutive unexplained miscarriages. Subjects received either IVIG 500 mg/kg or the equivalent volume of normal saline. Preconception infusions were administered 14–21 days from the projected next menstrual period. With documentation of pregnancy, the subject received the same infusion every 4 weeks until 18–20 weeks of gestation. The primary outcome was an ongoing pregnancy of at least 20 weeks of gestation. RESULTS A total of 82 patients enrolled, of whom 47 had an index pregnancy. All ongoing pregnancies resulted in live births. Therefore, the live birth rates were 70% (16/23) in the IVIG group and 63% (15/24) in the control group (P = 0.760); odds ratio (OR) 1.37 [95% confidence interval (CI) 0.41–4.61]. Including only clinical pregnancies (embryo with cardiac activity at 6 weeks of gestation), the live birth rates were equivalent, 94% (16/17) and (15/16), respectively (P > 0.999); OR 1.07 (95% CI 0.06–18.62). Meta-analysis of randomized controlled trials (RCTs) evaluating IVIG for idiopathic secondary recurrent miscarriage revealed live birth rates of 70% (31/44) in the IVIG group and 62% (28/45) in the control group (P = 0.503); common OR 1.44 (95% CI 0.59–3.48). CONCLUSIONS This is the largest RCT to date in which IVIG was evaluated in women with idiopathic secondary recurrent miscarriage; no treatment benefit was found. The meta-analysis, which combined our study

HLA-DRB1 alleles and juvenile idiopathic arthritis: Diagnostic clues emerging from a meta-analysis.

PubMed

De Silvestri, Annalisa; Capittini, Cristina; Poddighe, Dimitri; Marseglia, Gian Luigi; Mascaretti, Luca; Bevilacqua, Elena; Scotti, Valeria; Rebuffi, Chiara; Pasi, Annamaria; Martinetti, Miryam; Tinelli, Carmine

2017-12-01

Juvenile Idiopathic Arthritis (JIA) is characterized with a variable pattern of articular involvement and systemic symptoms and, thus, it has been classified in several subtypes. Genetic predisposition to JIA is mainly due to HLA class II molecules (HLA-DRB1, HLA-DPB1), although HLA class I molecules and non-HLA genes have been implicated, too. Here, we carried out a meta-analysis including selected studies designed to assess HLA genetic background of JIA patients, compared to healthy controls; particularly, we focused our attention on HLA-DRB1. In summary, our meta-analysis showed four main findings regarding HLA-DRB1 locus as a genetic factor of JIA: i) HLA-DRB1*08 is a strong factor predisposing to JIA, both for oligo-articular and poly-articular forms (oJIA>pJIA); ii) HLA-DRB1*01 and HLA-DRB1*04 may be involved in the genetic predisposition of Rheumatoid Factor (RF) positive forms of JIA; iii) HLA-DRB1*11 was confirmed to be predisposing to oligo-articular JIA; iv) HLA-DRB1*04 was confirmed to have a role in systemic JIA. Importantly, RF positivity seems to select the JIA clinical subset with the strongest immunogenetic similarities with adult rheumatoid arthritis. Copyright © 2017 Elsevier B.V. All rights reserved.

[Uveitis associated with juvenile idiopathic arthritis : Optimization of immunomodulatory therapy].

PubMed

Heiligenhaus, A; Tappeiner, C; Walscheid, K; Heinz, C

2016-05-01

Uveitis associated with juvenile idiopathic arthritis (JIA-associated uveitis) is a vision-threatening disorder with a high complication rate. Besides early diagnosis within screening programs an adequate therapy is essential for improvement of the long-term prognosis. Corticosteroid therapy is often insufficient. In addition to conventional immunosuppression, immunomodulatory drugs, so-called biologicals, are novel highly effective treatment modalities. A systematic search of the literature was carried out for biologicals currently used in the treatment of JIA-associated uveitis. Review of current publications, summary of treatment guidelines and discussion of treatment options for therapy refractive patients. In accordance with the current recommendations tumor necrosis factor (TNF) inhibitors are administered if uveitis inactivity cannot be achieved with topical corticosteroids and in the next stage with immunosuppressants (methotrexate preferred). According to the currently available data adalimumab is then preferred. When the effectiveness of TNF inhibitors ceases during long-term administration and/or recurrences, other biological response modifiers are attractive treatment options (e. g. lymphocyte inhibitors or specific receptor antagonists). The TNF inhibitors are of major importance for the treatment of JIA-associated uveitis. Prospective studies and registries would be desirable in order to be able to compare the value of TNF inhibitors and other biologicals and for optimization of treatment recommendations.

VibroCV: a computer vision-based vibroarthrography platform with possible application to Juvenile Idiopathic Arthritis.

PubMed

Wiens, Andrew D; Prahalad, Sampath; Inan, Omer T

2016-08-01

Vibroarthrography, a method for interpreting the sounds emitted by a knee during movement, has been studied for several joint disorders since 1902. However, to our knowledge, the usefulness of this method for management of Juvenile Idiopathic Arthritis (JIA) has not been investigated. To study joint sounds as a possible new biomarker for pediatric cases of JIA we designed and built VibroCV, a platform to capture vibroarthrograms from four accelerometers; electromyograms (EMG) and inertial measurements from four wireless EMG modules; and joint angles from two Sony Eye cameras and six light-emitting diodes with commercially-available off-the-shelf parts and computer vision via OpenCV. This article explains the design of this turn-key platform in detail, and provides a sample recording captured from a pediatric subject.

Clinical management algorithm of uveitis associated with juvenile idiopathic arthritis: interdisciplinary panel consensus.

PubMed

Bou, Rosa; Adán, Alfredo; Borrás, Fátima; Bravo, Beatriz; Calvo, Inmaculada; De Inocencio, Jaime; Díaz, Jesús; Escudero, Julia; Fonollosa, Alex; de Vicuña, Carmen García; Hernández, Victoria; Merino, Rosa; Peralta, Jesús; Rúa, María-Jesús; Tejada, Pilar; Antón, Jordi

2015-05-01

Uveitis associated with juvenile idiopathic arthritis (JIA) typically involves the anterior chamber segment, follows an indolent chronic course, and presents a high rate of uveitic complications and a worse outcome as compared to other aetiologies of uveitis. Disease assessment, treatment, and outcome measures have not been standardized. Collaboration between pediatric rheumatologists and ophthalmologists is critical for effective management and prevention of morbidity, impaired vision, and irreparable visual loss. Although the Standardization of Uveitis Nomenclature Working Group recommendations have been a great advance to help clinicians to improve consistency in grading and reporting data, difficulties arise at the time of deciding the best treatment approach in the individual patient in routine daily practice. For this reason, recommendations for a systematized control and treatment strategies according to clinical characteristics and disease severity in children with JIA-related uveitis were developed by a panel of experts with special interest in uveitis associated with JIA. A clinical management algorithm organized in a stepwise regimen is here presented.

Is hydrotherapy cost-effective? A randomised controlled trial of combined hydrotherapy programmes compared with physiotherapy land techniques in children with juvenile idiopathic arthritis.

PubMed

Epps, H; Ginnelly, L; Utley, M; Southwood, T; Gallivan, S; Sculpher, M; Woo, P

2005-10-01

To compare the effects of combined hydrotherapy and land-based physiotherapy (combined) with land-based physiotherapy only (land) on cost, health-related quality of life (HRQoL) and outcome of disease in children with juvenile idiopathic arthritis (JIA). Also to determine the cost-effectiveness of combined hydrotherapy and land-based physiotherapy in JIA. A multicentre randomised controlled, partially blinded trial was designed with 100 patients in a control arm receiving land-based physiotherapy only (land group) and 100 patients in an intervention arm receiving a combination of hydrotherapy and land-based physiotherapy (combined group). Three tertiary centres in the UK. Patients aged 4-19 years diagnosed more than 3 months with idiopathic arthritides, onset before their 16th birthday, stable on medication with at least one active joint. Patients in the combined and land groups received 16 1-hour treatment sessions over 2 weeks followed by local physiotherapy attendances for 2 months. Disease improvement defined as a decrease of > or =30% in any three of six core set variables without there being a 30% increase in more than one of the remaining three variables was used as the primary outcome measure and assessed at 2 months following completion of intervention. Health services resource use (in- and outpatient care, GP visits, drugs, interventions, and investigations) and productivity costs (parents' time away from paid work) were collected at 6 months follow-up. HRQoL was measured at baseline and 2 and 6 months following intervention using the EQ-5D, and quality-adjusted life-years (QALYs) were calculated. Secondary outcome measures at 2 and 6 months included cardiovascular fitness, pain, isometric muscle strength and patient satisfaction. Seventy-eight patients were recruited into the trial and received treatment. Two months after intervention 47% patients in the combined group and 61% patients in the land group had improved disease with 11 and 5% with worsened

Prior to extension, Transcriptomes of fibroblast-like Synoviocytes from extended and Polyarticular juvenile idiopathic arthritis are indistinguishable.

PubMed

Brescia, AnneMarie C; Simonds, Megan M; McCahan, Suzanne M; Sullivan, Kathleen E; Rose, Carlos D

2018-01-08

Our intent was to identify differences between the transcriptome of fibroblast-like synoviocytes (FLS) in oligoarticular juvenile idiopathic arthritis (JIA) before extension when compared to persistent subtype of JIA, when the two are clinically indistinguishable. Additionally, we sought to determine if differences between the transcriptomes of FLS from extended-to-be and polyarticular course JIA could be detected. Our hypothesis was that intrinsic differences in the transcriptome of the FLS from extended-to-be JIA would distinguish them from persistent oligoarticular JIA, before the course is clinically apparent. Global gene expression was defined in cultured FLS from 6 controls, 12 JIA with persistent course, 7 JIA prior to extension (extended-to-be), 4 JIA with extended course and 6 polyarticular onset, using Affymetrix Human GeneChips 133plus2.0. Bioconductor Linear Models for Microarray Analysis revealed 22 probesets with differential expression between persistent and extended-to-be FLS at 15% FDR, however only 2 probesets distinguished extended-to-be from extended and none distinguished extended-to-be and polyarticular at 15% FDR. Differences in extended and polyarticular gene expression profiles were not detected. Confirmation of select genes was done on the RNA level by RT-qPCR and on the protein level in synovial fluid by ELISA. The transcriptome of FLS from extended-to-be juvenile idiopathic arthritis is distinct from persistent course before a clinical distinction can be made. Additionally, the transcriptome of extended-to-be and polyarticular course, including those who have already extended, are indistinguishable. These gene expression data suggest that FLS already reflect a polyarticular behavior early in disease course, suggesting that extended-to-be may be "latent polyarticular" at onset. These differences can be used to develop early biomarkers of disease course, allowing for better-informed treatment decisions.

Contrast-enhanced MRI compared with the physical examination in the evaluation of disease activity in juvenile idiopathic arthritis.

PubMed

Hemke, Robert; Maas, Mario; van Veenendaal, Mira; Dolman, Koert M; van Rossum, Marion A J; van den Berg, J Merlijn; Kuijpers, Taco W

2014-02-01

To assess the value of magnetic resonance imaging (MRI) in discriminating between active and inactive juvenile idiopathic arthritis (JIA) patients and to compare physical examination outcomes with MRI outcomes in the assessment of disease status in JIA patients. Consecutive JIA patients with knee involvement were prospectively studied using an open-bore MRI. Imaging findings from 146 JIA patients were analysed (59.6% female; mean age, 12.9 years). Patients were classified as clinically active or inactive. MRI features were evaluated using the JAMRIS system, comprising validated scores for synovial hypertrophy, bone marrow oedema, cartilage lesions and bone erosions. Inter-reader reliability was good for all MRI features (intra-class correlation coefficient [ICC] = 0.87-0.94). No differences were found between the two groups regarding MRI scores of bone marrow oedema, cartilage lesions or bone erosions. Synovial hypertrophy scores differed significantly between groups (P = 0.016). Nonetheless, synovial hypertrophy was also present in 14 JIA patients (35.9%) with clinically inactive disease. Of JIA patients considered clinically active, 48.6% showed no signs of MRI-based synovitis. MRI can discriminate between clinically active and inactive JIA patients. However, physical examination is neither very sensitive nor specific in evaluating JIA disease activity compared with MRI. Subclinical synovitis was present in >35% of presumed clinically inactive patients. • MRI is sensitive for evaluating juvenile idiopathic arthritis (JIA) disease activity. • Contrast-enhanced MRI can distinguish clinically active and inactive JIA patients. • Subclinical synovitis is present in 35.9 % of presumed clinically inactive patients. • Physical examination is neither sensitive nor specific in evaluating JIA disease activity.

Physical Examination Tools Used to Identify Swollen and Tender Lower Limb Joints in Juvenile Idiopathic Arthritis: A Scoping Review.

PubMed

Fellas, Antoni; Singh-Grewal, Davinder; Santos, Derek; Coda, Andrea

2018-01-01

Juvenile idiopathic arthritis (JIA) is the most common form of rheumatic disease in childhood and adolescents, affecting between 16 and 150 per 100,000 young persons below the age of 16. The lower limb is commonly affected in JIA, with joint swelling and tenderness often observed as a result of active synovitis. The objective of this scoping review is to identify the existence of physical examination (PE) tools to identify and record swollen and tender lower limb joints in children with JIA. Two reviewers individually screened the eligibility of titles and abstracts retrieved from the following online databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL. Studies that proposed and validated a comprehensive lower limb PE tool were included in this scoping review. After removal of duplicates, 1232 citations were retrieved, in which twelve were identified as potentially eligible. No studies met the set criteria for inclusion. Further research is needed in developing and validating specific PE tools for clinicians such as podiatrists and other allied health professionals involved in the management of pathological lower limb joints in children diagnosed with JIA. These lower limb PE tools may be useful in conjunction with existing disease activity scores to optimise screening of the lower extremity and monitoring the efficacy of targeted interventions.

A methodological approach for assessing the uptake of core outcome sets using ClinicalTrials.gov: findings from a review of randomised controlled trials of rheumatoid arthritis.

PubMed

Kirkham, Jamie J; Clarke, Mike; Williamson, Paula R

2017-05-17

Objective  To assess the uptake of the rheumatoid arthritis core outcome set using a new assessment method of calculating uptake from data in clinical trial registry entries. Design  Review of randomised trials. Setting  ClinicalTrials.gov. Subjects  273 randomised trials of drug interventions for the treatment of rheumatoid arthritis and registered in ClinicalTrials.gov between 2002 and 2016. Full publications were identified for completed studies from information in the trial registry or from an internet search using Google and the citation database Web of Science. Main outcome measure  The percentage of trials reporting or planning to measure the rheumatoid arthritis core outcome set calculated from the information presented in the trial registry and compared with the percentage reporting the rheumatoid arthritis core outcome set in the resulting trial publications. Results  The full rheumatoid arthritis core outcome set was reported in 81% (116/143) of trials identified on the registry as completed (or terminated) for which results were found in either the published literature or the registry. For trials identified on the registry as completed (or terminated), using information only available in the registry gives an estimate for uptake of 77% (145/189). Conclusions  The uptake of the rheumatoid arthritis core outcome set in clinical trials has continued to increase over time. Using the information on outcomes listed for completed or terminated studies in a trial registry provides a reasonable estimate of the uptake of a core outcome set and is a more efficient and up-to-date approach than examining the outcomes in published trial reports. The method proposed may provide an efficient approach for an up-to-date assessment of the uptake of the 300 core outcome sets already published. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Genome Engineering for Personalized Arthritis Therapeutics.

PubMed

Adkar, Shaunak S; Brunger, Jonathan M; Willard, Vincent P; Wu, Chia-Lung; Gersbach, Charles A; Guilak, Farshid

2017-10-01

Arthritis represents a family of complex joint pathologies responsible for the majority of musculoskeletal conditions. Nearly all diseases within this family, including osteoarthritis, rheumatoid arthritis, and juvenile idiopathic arthritis, are chronic conditions with few or no disease-modifying therapeutics available. Advances in genome engineering technology, most recently with CRISPR-Cas9, have revolutionized our ability to interrogate and validate genetic and epigenetic elements associated with chronic diseases such as arthritis. These technologies, together with cell reprogramming methods, including the use of induced pluripotent stem cells, provide a platform for human disease modeling. We summarize new evidence from genome-wide association studies and genomics that substantiates a genetic basis for arthritis pathogenesis. We also review the potential contributions of genome engineering in the development of new arthritis therapeutics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Joint cartilage thickness and automated determination of bone age and bone health in juvenile idiopathic arthritis.

PubMed

Twilt, Marinka; Pradsgaard, Dan; Spannow, Anne Helene; Horlyck, Arne; Heuck, Carsten; Herlin, Troels

2017-08-10

BoneXpert is an automated method to calculate bone maturation and bone health index (BHI) in children with juvenile idiopathic arthritis (JIA). Cartilage thickness can also be seen as an indicator for bone health and arthritis damage. The objective of this study was to evaluate the relation between cartilage thickness, bone maturation and bone health in patients with JIA. Patients with JIA diagnosed according ILAR criteria included in a previous ultrasonography (US) study were eligible if hand radiographs were taken at the same time as the US examination. Of the 95 patients 67 met the inclusion criteria. Decreased cartilage thickness was seen in 27% of the examined joints. Decreased BHI was seen in half of the JIA patient, and delayed bone maturation was seen in 33% of patients. A combination of decreased BHI and bone age was seen in 1 out of 5 JIA patients. Decreased cartilage thickness in the knee, wrist and MCP joint was negatively correlated with delayed bone maturation but not with bone health index. Delayed bone maturation and decreased BHI were not related to a thinner cartilage, but a thicker cartilage. No relation with JADAS 10 was found. The rheumatologist should remain aware of delayed bone maturation and BHI in JIA patients with cartilage changes, even in the biologic era.

A protocol for a randomised controlled trial of prefabricated versus customised foot orthoses for people with rheumatoid arthritis: the FOCOS RA trial [Foot Orthoses - Customised v Off-the-Shelf in Rheumatoid Arthritis].

PubMed

Gallagher, Kellie S; Godwin, Jon; Hendry, Gordon J; Steultjens, Martijn; Woodburn, Jim

2018-01-01

Foot pain is common in rheumatoid arthritis and appears to persist despite modern day medical management. Several clinical practice guidelines currently recommend the use of foot orthoses for the treatment of foot pain in people with rheumatoid arthritis. However, an evidence gap currently exists concerning the comparative clinical- and cost-effectiveness of prefabricated and customised foot orthoses in people with early rheumatoid arthritis. Early intervention with orthotics may offer the best opportunity for positive therapeutic outcomes. The primary aim of this study is to evaluate the comparative clinical- and cost-effectiveness of prefabricated versus customised orthoses for reducing foot pain over 12 months. This is a multi-centre two-arm parallel randomised controlled trial comparing prefabricated versus customised orthoses in participants with early rheumatoid arthritis (< 2 years disease duration). A total of 160 (a minimum of 80 randomised to each arm) eligible participants will be recruited from United Kingdom National Health Service Rheumatology Outpatient Clinics. The primary outcome will be foot pain measured via the Foot Function Index pain subscale at 12 months. Secondary outcomes will include foot related impairments and disability via the Foot Impact Scale for rheumatoid arthritis, global functional status via the Stanford Health Assessment Questionnaire, foot disease activity via the Rheumatoid Arthritis Foot Disease Activity Index, and health-related quality of life at baseline, 6 and 12 months. Process outcomes will include recruitment/retention rates, data completion rates, intervention adherence rates, and participant intervention and trial participation satisfaction. Cost-utility and cost-effectiveness analyses will be undertaken. Outcome measures collected at baseline, 6 and 12 months will be used to evaluate the comparative clinical- and cost- effectiveness of customised versus prefabricated orthoses for this treatment of early

The effects of arthritis gloves on people with Rheumatoid Arthritis or Inflammatory Arthritis with hand pain: a study protocol for a multi-centre randomised controlled trial (the A-GLOVES trial).

PubMed

Prior, Yeliz; Sutton, Chris; Cotterill, Sarah; Adams, Jo; Camacho, Elizabeth; Arafin, Nazina; Firth, Jill; O'Neill, Terence; Hough, Yvonne; Jones, Wendy; Hammond, Alison

2017-05-30

Arthritis gloves are regularly provided as part of the management of people with rheumatoid arthritis (RA) and undifferentiated (early) inflammatory arthritis (IA). Usually made of nylon and elastane (i.e. Lycra®), these arthritis gloves apply pressure with the aims of relieving hand pain, stiffness and improving hand function. However, a systematic review identified little evidence supporting their use. We therefore designed a trial to compare the effectiveness of the commonest type of arthritis glove provided in the United Kingdom (Isotoner gloves) (intervention) with placebo (control) gloves (i.e. larger arthritis gloves providing similar warmth to the intervention gloves but minimal pressure only) in people with these conditions. Participants aged 18 years and over with RA or IA and persistent hand pain will be recruited from National Health Service Trusts in the United Kingdom. Following consent, participants will complete a questionnaire booklet, then be randomly allocated to receive intervention or placebo arthritis gloves. Within three weeks, they will be fitted with the allocated gloves by clinical specialist rheumatology occupational therapists. Twelve weeks (i.e. the primary endpoint) after completing the baseline questionnaire, participants will complete a second questionnaire, including the same measures plus additional questions to explore adherence, benefits and problems with glove-wear. A sub-sample of participants from each group will be interviewed at the end of their participation to explore their views of the gloves received. The clinical effectiveness and cost-effectiveness of the intervention, compared to placebo gloves, will be evaluated over 12 weeks. The primary outcome measure is hand pain during activity. Qualitative interviews will be thematically analysed. This study will evaluate the commonest type of arthritis glove (Isotoner) provided in the NHS (i.e. the intervention) compared to a placebo glove. The results will help

Long-term treatment with rituximab in severe juvenile idiopathic arthritis-associated uveitis.

PubMed

Miserocchi, Elisabetta; Modorati, Giulio; Berchicci, Luigi; Pontikaki, Irene; Meroni, Pierluigi; Gerloni, Valeria

2016-06-01

To evaluate retrospectively the long-term efficacy of rituximab in patients with severe juvenile idiopathic arthritis (JIA)-associated uveitis. Eight patients (15 eyes) with severe and longstanding JIA uveitis, who had an inadequate response in controlling uveitis to one or more biologic agents including tumour necrosis factor blockers and abatacept, received rituximab therapy. Rituximab was given at a dose of 1000 mg per infusion on days 1 and 15 and then every 6 months. Clinical responses to treatment, including decrease in uveitis activity, visual acuity changes, reduction of concomitant local and systemic corticosteroid and/or immunosuppressants, and occurrence of adverse events, were assessed. Eight patients with a mean±SD age of 22.8±5.5 years were treated. The mean ocular disease duration was 17.7 years; the mean±SD follow-up time on rituximab was 44.75±4.9 months; and the mean number of rituximab infusions received was 8.75 (range 6-12). All patients achieved complete control of uveitis, but in two patients rituximab was discontinued due to inefficacy in treating arthritis. The decrease in uveitis activity was evident 4-5 months after the first infusion. Systemic corticosteroids and immunosuppressants used in association with rituximab were discontinued in five patients at the end of follow-up. None of the patients experienced visual worsening during the follow-up. No drug-related complications were encountered. Rituximab may be a promising effective treatment option for refractory uveitis associated with JIA leading to long-term quiescence of uveitis, particularly for patients who have not previously responded to other biologic therapies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Concealed concern: fathers' experiences of having a child with juvenile idiopathic arthritis.

PubMed

Waite-Jones, J M; Madill, A

2008-01-01

Despite increased research into families of chronically ill children, more needs to be known about the father's experience. We address this issue through asking: 'What is it like to be the father of a child with Juvenile Idiopathic Arthritis?' (JIA). Four members of eight families with an adolescent diagnosed with JIA, including seven fathers, were interviewed and transcripts analysed using grounded theory. This study suggests that fathers of children with JIA experience several severe losses which are exacerbated through comparisons they make between their own situation and that of fathers of healthy children. In addition, the fathers faced several constraints which reduced their opportunities to communicate with their ill child through shared activities. Fathers appeared to conceal their distress by adopting strategies of denial and distraction however their adjustment was facilitated, to some extent, by social support. They could also develop greater acceptance of their situation over time as the care of their ill child became assimilated into family life and constraints upon their life gradually reduced through the increased maturity of their son or daughter with JIA. These findings have implications for healthcare professionals and voluntary organisations.

Caregiver recall of treatment recommendations in juvenile idiopathic arthritis.

PubMed

De Civita, Mirella; Feldman, Debbie Ehrmann; Meshefedjian, Garbis A; Dobkin, Patricia L; Malleson, Pete; Duffy, Ciarán M

2007-03-15

Health care providers in juvenile idiopathic arthritis (JIA) might refer to caregivers' self-report of children's treatment-related behaviors to assist in clinical decisions. However, caregivers may believe that they are adhering to treatment even though they have a different understanding of recommendations than that intended by the medical team. We examined whether caregiver recall of children's JIA treatment matched actual recommendations at baseline and 3, 6, 9, and 12 months. A total of 235 primary caregivers were recruited from rheumatology clinics at 2 pediatric university-based teaching hospitals in Canada. Using the Parent Adherence Report Questionnaire, caregivers indicated whether their child was prescribed medications and/or exercises. Medical charts were reviewed to determine the prescribed treatment. Level of agreement between both sets of data was then examined. A total of 175 caregivers provided complete data. Mean age of the children was 10.2 years (68.6% girls); 44.6% were diagnosed with oligoarthritis. Kappa coefficients for medication represented substantial to almost perfect agreement beyond chance, with better levels of agreement at 12 months (kappa = 0.81, 95% confidence interval [95% CI] 0.68, 0.94) than at baseline (kappa = 0.61, 95% CI 0.47, 0.76). Kappa coefficients for exercise represented slight to moderate agreement beyond chance, with better agreement at 12 months (kappa = 0.44, 95% CI 0.24, 0.63) than at baseline (kappa = 0.27, 95% CI 0.08, 0.47). Weaker agreement for the exercise regimen raises concern that caregivers may pay less attention to exercise recommendations or that these recommendations may not be easily understood.

PADI4 and the HLA-DRB1 shared epitope in juvenile idiopathic arthritis.

PubMed

Hisa, Kaori; Yanagimachi, Masakatsu D; Naruto, Takuya; Miyamae, Takako; Kikuchi, Masako; Hara, Rhoki; Imagawa, Tomoyuki; Yokota, Shumpei; Mori, Masaaki

2017-01-01

Both genetic and environmental factors are associated with susceptibility to juvenile idiopathic arthritis (JIA). Many studies have reported that both a 'shared epitope' (SE) encoded by several HLA-DRB1 alleles and the peptidyl arginine deiminase type 4 (PADI4) gene polymorphisms are associated with susceptibility to rheumatoid arthritis (RA). However, it is uncertain whether JIA and RA share the latter genetic risk factor. Therefore, here we investigated relationships between HLA-SE and PADI4 polymorphisms with clinical subtypes of JIA. JIA patients (39 oligoarthritis, 48 RF-positive polyarthritis, 19 RF-negative polyarthritis and 82 systemic) and 188 healthy controls were genotyped for HLA-DRB1 by PCR-sequence-specific oligonucleotide probe methodology. Three PADI4 gene single nucleotide polymorphisms (SNPs), rs2240340, rs2240337 and rs1748033, were genotyped using TaqMan SNP Genotyping Assays. Frequencies of the HLA-SE were higher in RF-positive polyarticular JIA than in healthy controls. RF-positive polyarticular JIA was associated with HLA-SE (OR = 5.3, 95% CI = 2.5-11.9, pc < 0.001). No associations were found between clinical subtypes of JIA and PADI4 allele frequency. Nonetheless, rs2240337 in the PADI4 gene was significantly associated with anti-cyclic citrullinated peptide antibody (ACPA)-positivity in JIA. The A allele at rs2240337 was a significant risk factor for ACPA positivity in JIA (OR = 5.6, 95% CI = 1.71-23.7 pc = 0.03). PADI4 gene polymorphism is associated with ACPA-positivity in JIA. The association of HLA-SE with RF-positive polyarticular JIA as well as RA is confirmed in Japanese. Thus, HLA-SE and PADI4 status both influence JIA clinical manifestations.

US trends in rates of arthroplasty for inflammatory arthritis including rheumatoid arthritis, juvenile idiopathic arthritis, and spondyloarthritis.

PubMed

Mertelsmann-Voss, Christina; Lyman, Stephen; Pan, Ting Jung; Goodman, Susan M; Figgie, Mark P; Mandl, Lisa A

2014-06-01

Although rates of arthroplasty have increased dramatically, rates among patients with rheumatoid arthritis (RA) are reported to be decreasing. It is not known if this is also the case among patients with other inflammatory arthritides. This study was undertaken to evaluate rates of arthroplasty due to RA, juvenile idiopathic arthritis (JIA), spondyloarthritis (SpA), and a composite group of patients with inflammatory arthritides (IA), compared to arthroplasty rates among patients without inflammatory or autoimmune conditions. Administrative discharge databases (State Inpatient Databases of the Healthcare Cost and Utilization Project, New York Department of Health Statewide Planning and Research Cooperative System, California Statewide Health Planning and Development) were used to compare rates of knee, hip, and shoulder arthroplasty occurring from 1991 to 2005. Of 2,839,325 arthroplasties in 1991-2005, 2.7% were performed in patients with IA. The rate of arthroplasty for noninflammatory conditions doubled (124.5 per 100,000 persons in 1991 versus 247.5 per 100,000 persons in 2005), while the rate for IA remained stable at 5.1 per 100,000. Rates of arthroplasty for RA decreased slightly (4.6 per 100,000 versus 4.5 per 100,000) and those for JIA decreased by nearly 50% (0.22 per 100,000 versus 0.13 per 100,000), but the rate of arthroplasty for SpA increased by nearly 50% (0.22 per 100,000 versus 0.31 per 100,000). Age at the time of arthroplasty increased for patients with RA (mean ± SD 63.4 ± 12.7 years versus 64.9 ± 12.8 years), JIA (30.9 ± 12.2 years versus 36.7 ± 14.9 years), and SpA (54.3 ± 16.1 years versus 60.4 ± 13.9 years). However, the mean age at the time of arthroplasty among non-IA cases decreased (71.5 ± 11.8 years versus 69.0 ± 12.0 years). This population-based study is the first to show that arthroplasty rates have decreased significantly among patients with JIA and minimally among patients with RA, and have increased among patients with Sp

CONTRAIS: CONservative TReatment for Adolescent Idiopathic Scoliosis: a randomised controlled trial protocol

PubMed Central

2013-01-01

Background Idiopathic scoliosis is a three-dimensional structural deformity of the spine that occurs in children and adolescents. Recent reviews on bracing and exercise treatment have provided some evidence for effect of these interventions. The purpose of this study is to improve the evidence base regarding the effectiveness of conservative treatments for preventing curve progression in idiopathic scoliosis. Methods/design Patients: Previously untreated girls and boys with idiopathic scoliosis, 9 to 17 years of age with at least one year of remaining growth and a curve Cobb angle of 25–40 degrees will be included. A total of 135 participants will be randomly allocated in groups of 45 patients each to receive one of the three interventions. Interventions: All three groups will receive a physical activity prescription according to the World Health Organisation recommendations. One group will additionally wear a hyper-corrective night-time brace. One group will additionally perform postural scoliosis-specific exercises. Outcome: Participation in the study will last until the curve has progressed, or until cessation of skeletal growth. Outcome variables will be measured every 6 months. The primary outcome variable, failure of treatment, is defined as progression of the Cobb angle more than 6 degrees, compared to the primary x-ray, seen on two consecutive spinal standing x-rays taken with 6 months interval. Secondary outcome measures include the SRS-22r and EQ5D-Y quality of life questionnaires, the International Physical Activity Questionnaire (IPAQ) short form, and Cobb angle at end of the study. Discussion This trial will evaluate which of the tested conservative treatment approaches that is the most effective for patients with adolescent idiopathic scoliosis. Trial registration NCT01761305 PMID:24007599

Ottawa Panel Evidence-Based Clinical Practice Guidelines for Structured Physical Activity in the Management of Juvenile Idiopathic Arthritis.

PubMed

Cavallo, Sabrina; Brosseau, Lucie; Toupin-April, Karine; Wells, George A; Smith, Christine A; Pugh, Arlanna G; Stinson, Jennifer; Thomas, Roanne; Ahmed, Sara; Duffy, Ciarán M; Rahman, Prinon; Àlvarez-Gallardo, Inmaculada C; Loew, Laurianne; De Angelis, Gino; Feldman, Debbie Ehrmann; Majnemer, Annette; Gagnon, Isabelle J; Maltais, Désirée; Mathieu, Marie-Ève; Kenny, Glen P; Tupper, Susan; Whitney-Mahoney, Kristi; Bigford, Sarah

2017-05-01

To create guidelines focused on the use of structured physical activity (PA) in the management of juvenile idiopathic arthritis (JIA). A systematic literature search was conducted using the electronic databases Cochrane Central Register of Controlled Trials, MEDLINE (Ovid), EMBASE (Ovid), and Physiotherapy Evidence Database for all studies related to PA programs for JIA from January 1966 until December 2014, and was updated in May 2015. Study selection was completed independently by 2 reviewers. Studies were included if they involved individuals aged ≤21 years diagnosed with JIA who were taking part in therapeutic exercise or other PA interventions for which effects of various disease-related outcomes were compared with a control group (eg, no PA program or activity of lower intensity). Two reviewers independently extracted information on interventions, comparators, outcomes, time period, and study design. The statistical analysis was reported using the Cochrane Collaboration methods. The quality of the included studies was assessed according to the Physiotherapy Evidence Database Scale. Five randomized controlled trials (RCTs) fit the selection criteria; of these, 4 were high-quality RCTs. The following recommendations were developed: (1) Pilates for improving quality of life, pain, functional ability, and range of motion (ROM) (grade A); (2) home exercise program for improving quality of life and functional ability (grade A); (3) aquatic aerobic fitness for decreasing the number of active joints (grade A); and (4) and cardio-karate aerobic exercise for improving ROM and number of active joints (grade C+). The Ottawa Panel recommends the following structured exercises and physical activities for the management of JIA: Pilates, cardio-karate, home and aquatic exercises. Pilates showed improvement in a higher number of outcomes. Copyright © 2017. Published by Elsevier Inc.

Clinical and MRI outcome of cervical spine lesions in children with juvenile idiopathic arthritis treated with anti-TNFα drugs early in disease course.

PubMed

Ključevšek, Damjana; Emeršič, Nina; Toplak, Nataša; Avčin, Tadej

2017-05-15

The purpose of the study was to evaluate the clinical and magnetic resonance imaging (MRI) outcome of cervical spine arthritis in children with juvenile idiopathic arthritis (JIA), who received anti-TNFα early in the course of cervical spine arthritis. Medical charts and imaging of JIA patients with cervical spine involvement were reviewed in this retrospective study. Data, including age at disease onset, JIA type, disease activity, treatment and clinical outcome were collected. Initial and followup MRI examinations of cervical spine were performed according to the hospital protocol to evaluate the presence of inflammation and potential chronic/late changes. Fifteen JIA patients with MRI proved cervical spine inflammation (11 girls, 4 boys, median age 6.3y) were included in the study: 9 had polyarthritis, 3 extended oligoarthritis, 2 persistent oligoarthritis and 1 juvenile psoriatic arthritis. All children were initially treated with high-dose steroids and methotrexate. In addition, 11 patients were treated with anti-TNFα drug within 3 months, and 3 patients within 7 months of cervical spine involvement confirmed by MRI. Mean observation time was 2.9y, mean duration of anti-TNFα treatment was 2.2y. Last MRI showed no active inflammation in 12/15 children, allowing to stop biological treatment in 3 patients, and in 3/15 significant reduction of inflammation. Mild chronic changes were found on MRI in 3 children. Early treatment with anti-TNFα drugs resulted in significantly reduced inflammation or complete remission of cervical spine arthritis proved by MRI, and prevented the development of serious chronic/late changes. Repeated MRI examinations are suggested in the follow-up of JIA patients with cervical spine arthritis.

A randomized controlled trial examining Iyengar yoga for young adults with rheumatoid arthritis: a study protocol

PubMed Central

2011-01-01

Background Rheumatoid arthritis is a chronic, disabling disease that can compromise mobility, daily functioning, and health-related quality of life, especially in older adolescents and young adults. In this project, we will compare a standardized Iyengar yoga program for young people with rheumatoid arthritis to a standard care wait-list control condition. Methods/Design Seventy rheumatoid arthritis patients aged 16-35 years will be randomized into either the 6-week Iyengar yoga program (12 - 1.5 hour sessions twice weekly) or the 6-week wait-list control condition. A 20% attrition rate is anticipated. The wait-list group will receive the yoga program following completion of the first arm of the study. We will collect data quantitatively, using questionnaires and markers of disease activity, and qualitatively using semi-structured interviews. Assessments include standardized measures of general and arthritis-specific function, pain, mood, and health-related quality of life, as well as qualitative interviews, blood pressure/resting heart rate measurements, a medical exam and the assessment of pro-inflammatory cytokines. Data will be collected three times: before treatment, post-treatment, and two months following the treatment. Discussion Results from this study will provide critical data on non-pharmacologic methods for enhancing function in rheumatoid arthritis patients. In particular, results will shed light on the feasibility and potential efficacy of a novel intervention for rheumatoid arthritis symptoms, paving the way for a larger clinical trial. Trial Registration ClinicalTrials.gov NCT01096823 PMID:21255431

Readout-segmented multi-shot diffusion-weighted MRI of the knee joint in patients with juvenile idiopathic arthritis.

PubMed

Sauer, Alexander; Li, Mengxia; Holl-Wieden, Annette; Pabst, Thomas; Neubauer, Henning

2017-10-12

Diffusion-weighted MRI has been proposed as a new technique for imaging synovitis without intravenous contrast application. We investigated diagnostic utility of multi-shot readout-segmented diffusion-weighted MRI (multi-shot DWI) for synovial imaging of the knee joint in patients with juvenile idiopathic arthritis (JIA). Thirty-two consecutive patients with confirmed or suspected JIA (21 girls, median age 13 years) underwent routine 1.5 T MRI with contrast-enhanced T1w imaging (contrast-enhanced MRI) and with multi-shot DWI (RESOLVE, b-values 0-50 and 800 s/mm 2 ). Contrast-enhanced MRI, representing the diagnostic standard, and diffusion-weighted images at b = 800 s/mm 2 were separately rated by three independent blinded readers at different levels of expertise for the presence and the degree of synovitis on a modified 5-item Likert scale along with the level of subjective diagnostic confidence. Fourteen (44%) patients had active synovitis and joint effusion, nine (28%) patients showed mild synovial enhancement not qualifying for arthritis and another nine (28%) patients had no synovial signal alterations on contrast-enhanced imaging. Ratings by the 1st reader on contrast-enhanced MRI and on DWI showed substantial agreement (κ = 0.74). Inter-observer-agreement was high for diagnosing, or ruling out, active arthritis of the knee joint on contrast-enhanced MRI and on DWI, showing full agreement between 1st and 2nd reader and disagreement in one case (3%) between 1st and 3rd reader. In contrast, ratings in cases of absent vs. little synovial inflammation were markedly inconsistent on DWI. Diagnostic confidence was lower on DWI, compared to contrast-enhanced imaging. Multi-shot DWI of the knee joint is feasible in routine imaging and reliably diagnoses, or rules out, active arthritis of the knee joint in paediatric patients without the need of gadolinium-based i.v. contrast injection. Possibly due to "T2w shine-through" artifacts, DWI does not reliably

Body experiences, emotional competence, and psychosocial functioning in juvenile idiopathic arthritis.

PubMed

Bomba, Monica; Meini, Antonella; Molinaro, Anna; Cattalini, Marco; Oggiano, Silvia; Fazzi, Elisa; Neri, Francesca; Plebani, Alessandro; Nacinovich, Renata

2013-08-01

We investigated self-image, psychological functioning, and quality of life in children and adolescents with juvenile idiopathic arthritis (JIA). Thirty-nine children with JIA were compared with 80 healthy peers. We first administered the Human Figure Drawing Test (HFDT) to all subjects; children also completed standardized questionnaires evaluating health-related quality of life (PEDSQL 4.0 Generic Core Scales) and the main aspects of psychological functioning: anxiety (SAFA-A) and depression (CDI). Parents were asked to complete the Child Behaviour Checklist (CBCL) and the PEDSQL 4.0. For each patient with JIA, clinical notes were gathered and a global disease assessment (visual analog scale--VAS) was performed. Compared to healthy peers, patients with JIA reported reduced maturity quotients at HFDT, more depressive traits, greater anxiety, and lower health-related quality of life. Among the subjects with JIA, HFDT revealed that adolescents had a greater impairment in all areas investigated. Furthermore, there was a significant correlation between the physical well-being rated by VAS and the perception of poorer quality of life in patients, mostly in the psychosocial domains. Children and adolescents with JIA exhibit emotional difficulties and a delay of psychological development leading to low self-esteem, a distorted self-image, more anxiety and depression traits, and a worse quality of life, when compared to healthy subjects.

PADI4 and the HLA-DRB1 shared epitope in juvenile idiopathic arthritis

PubMed Central

Hisa, Kaori; Yanagimachi, Masakatsu D.; Naruto, Takuya; Miyamae, Takako; Kikuchi, Masako; Hara, Rhoki; Imagawa, Tomoyuki; Yokota, Shumpei; Mori, Masaaki

2017-01-01

Objective Both genetic and environmental factors are associated with susceptibility to juvenile idiopathic arthritis (JIA). Many studies have reported that both a ‘shared epitope’ (SE) encoded by several HLA-DRB1 alleles and the peptidyl arginine deiminase type 4 (PADI4) gene polymorphisms are associated with susceptibility to rheumatoid arthritis (RA). However, it is uncertain whether JIA and RA share the latter genetic risk factor. Therefore, here we investigated relationships between HLA-SE and PADI4 polymorphisms with clinical subtypes of JIA. Methods JIA patients (39 oligoarthritis, 48 RF-positive polyarthritis, 19 RF-negative polyarthritis and 82 systemic) and 188 healthy controls were genotyped for HLA-DRB1 by PCR-sequence-specific oligonucleotide probe methodology. Three PADI4 gene single nucleotide polymorphisms (SNPs), rs2240340, rs2240337 and rs1748033, were genotyped using TaqMan SNP Genotyping Assays. Results Frequencies of the HLA-SE were higher in RF-positive polyarticular JIA than in healthy controls. RF-positive polyarticular JIA was associated with HLA-SE (OR = 5.3, 95% CI = 2.5–11.9, pc < 0.001). No associations were found between clinical subtypes of JIA and PADI4 allele frequency. Nonetheless, rs2240337 in the PADI4 gene was significantly associated with anti-cyclic citrullinated peptide antibody (ACPA)-positivity in JIA. The A allele at rs2240337 was a significant risk factor for ACPA positivity in JIA (OR = 5.6, 95% CI = 1.71–23.7 pc = 0.03). Conclusion PADI4 gene polymorphism is associated with ACPA-positivity in JIA. The association of HLA-SE with RF-positive polyarticular JIA as well as RA is confirmed in Japanese. Thus, HLA-SE and PADI4 status both influence JIA clinical manifestations. PMID:28182665

Improving physical activity in arthritis clinical trial (IMPAACT): study design, rationale, recruitment, and baseline data.

PubMed

Chang, Rowland W; Semanik, Pamela A; Lee, Jungwha; Feinglass, Joseph; Ehrlich-Jones, Linda; Dunlop, Dorothy D

2014-11-01

Over 21 million Americans report an arthritis-attributable activity limitation. Knee osteoarthritis (OA) and rheumatoid arthritis (RA) are two of the most common/disabling forms of arthritis. Various forms of physical activity (PA) can improve a variety of health outcomes and reduce health care costs, but the proportion of the US population engaging in the recommended amount of PA is low and even lower among those with arthritis. The Improving Motivation for Physical Activity in Arthritis Clinical Trial (IMPAACT) is a randomized clinical trial that studied the effects of a lifestyle PA promotion intervention on pain and physical function outcomes. The IMPAACT intervention was based on a chronic care/disease management model in which allied health professionals promote patient self-management activities outside of traditional physician office encounters. The program was a motivational interviewing-based, individualized counseling and referral intervention, directed by a comprehensive assessment of individual patient barriers and strengths related to PA performance. The specific aims of IMPAACT were to test the efficacy of the IMPAACT intervention for persons with arthritis (N=185 persons with RA and 155 persons with knee OA) in improving arthritis-specific and generic self-reported pain and Physical Function outcomes, observed measures of function, and objectively measured and self-reported PA levels. Details of the stratified-randomized study design, subject recruitment, and data collection are described. The results from IMPAACT will generate empiric evidence pertaining to increasing PA levels in persons with arthritis and result in widely applicable strategies for health behavior change. Copyright © 2014 Elsevier Inc. All rights reserved.

Influence of etanercept on leptin and ghrelin secretion in children with juvenile idiopathic arthritis.

PubMed

Maciejewska-Paszek, Izabela; Grochowska-Niedworok, Elżbieta; Siwiec, Andrzej; Gruenpeter, Anna; Dul, Lechosław; Irzyniec, Tomasz

2017-04-01

Objective To assess possible changes in leptin and ghrelin secretion due to etanercept in juvenile idiopathic arthritis (JIA). Methods 50 patients with JIA and 16 age-matched controls were enrolled into this prospective, cross-sectional study. Serum leptin, total and acyl ghrelin were measured in addition to white blood cell (WBC) and lymphocyte counts. Results 25 patients received etanercept and 25 conventional therapies (including methotrexate) for JIA. There was no difference between treatment and control groups in leptin or ghrelin levels and no evidence of a relationship between leptin and ghrelin in patients with JIA. In all children with JIA there was a correlation between leptin and body mass index (BMI). However, compared with children in the conventional treatment group, children in the etanercept group showed a positive correlation between total ghrelin and BMI and those with a low BMI showed a negative correlation between acyl ghrelin and BMI. Conclusion No differences in leptin and ghrelin concentrations were found when patients with JIA and controls were compared or when patients who received etanercept were compared with those who received conventional treatment for JIA.

Long-term safety and efficacy of abatacept in children with juvenile idiopathic arthritis.

PubMed

Ruperto, Nicolino; Lovell, Daniel J; Quartier, Pierre; Paz, Eliana; Rubio-Pérez, Nadina; Silva, Clovis A; Abud-Mendoza, Carlos; Burgos-Vargas, Ruben; Gerloni, Valeria; Melo-Gomes, Jose A; Saad-Magalhães, Claudia; Chavez-Corrales, J; Huemer, Christian; Kivitz, Alan; Blanco, Francisco J; Foeldvari, Ivan; Hofer, Michael; Horneff, Gerd; Huppertz, Hans-Iko; Job-Deslandre, Chantal; Loy, Anna; Minden, Kirsten; Punaro, Marilynn; Nunez, Alejandro Flores; Sigal, Leonard H; Block, Alan J; Nys, Marleen; Martini, Alberto; Giannini, Edward H

2010-06-01

We previously documented that abatacept was effective and safe in patients with juvenile idiopathic arthritis (JIA) who had not previously achieved a satisfactory clinical response with disease-modifying antirheumatic drugs or tumor necrosis factor blockade. Here, we report results from the long-term extension (LTE) phase of that study. This report describes the long-term, open-label extension phase of a double-blind, randomized, controlled withdrawal trial in 190 patients with JIA ages 6-17 years. Children were treated with 10 mg/kg abatacept administered intravenously every 4 weeks, with or without methotrexate. Efficacy results were based on data derived from the 153 patients who entered the open-label LTE phase and reflect >or=21 months (589 days) of treatment. Safety results include all available open-label data as of May 7, 2008. Of the 190 enrolled patients, 153 entered the LTE. By day 589, 90%, 88%, 75%, 57%, and 39% of patients treated with abatacept during the double-blind and LTE phases achieved responses according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, Pedi 70, Pedi 90, and Pedi 100 criteria for improvement, respectively. Similar response rates were observed by day 589 among patients previously treated with placebo. Among patients who had not achieved an ACR Pedi 30 response at the end of the open-label lead-in phase and who proceeded directly into the LTE, 73%, 64%, 46%, 18%, and 5% achieved ACR Pedi 30, Pedi 50, Pedi 70, Pedi 90, and Pedi 100 responses, respectively, by day 589 of the LTE. No cases of tuberculosis and no malignancies were reported during the LTE. Pneumonia developed in 3 patients, and multiple sclerosis developed in 1 patient. Abatacept provided clinically significant and durable efficacy in patients with JIA, including those who did not initially achieve an ACR Pedi 30 response during the initial 4-month open-label lead-in phase.

Alarmins firing arthritis: Helpful diagnostic tools and promising therapeutic targets.

PubMed

Lavric, Miha; Miranda-García, María Auxiliadora; Holzinger, Dirk; Foell, Dirk; Wittkowski, Helmut

2017-07-01

Alarmins are endogenous molecules with homeostatic roles that have reached the focus of research in inflammatory arthritis in the last two decades, mostly due to their ability to indicate tissue related damage after active or passive release from injured cells. From HMGB1, S100A8/A9 and S100A12 proteins, over heat-shock proteins (HSPs) and purine metabolites (e.g. uric acid, ATP) to altered matrix proteins and interleukin-33 (IL-33), a number of alarmins have been determined until now as having a role in rheumatoid arthritis, psoriatic and juvenile idiopathic arthritis, as well as spondyloarthritis and gout. Although formerly being linked to initiation and chronification of inflammatory arthritis, driving auto- and paracrine inflammatory loops, more recent research has also unraveled the alarmins' role in the crosstalk between innate and adaptive immunity and in resolution of inflammation. Providing a state-of-the-art overview of known alarmins, this review lists the known modes of action and pathologic contribution of alarmins to inflammatory arthritis, as well as biomarker potential of alarmins in the clinical setting for tracking disease severity. Based upon research on animal experimental models (CIA, AIA) and clinical trials, a look is made into potentially viable strategies for modifying alarmin secretion and their target receptor (e.g. TLR, RAGE) interaction with the purpose of attenuating arthritic disease. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Clinical features of children with enthesitis-related juvenile idiopathic arthritis / juvenile spondyloarthritis followed in a French tertiary care pediatric rheumatology centre.

PubMed

Goirand, Maxime; Breton, Sylvain; Chevallier, Frédéric; Duong, Ngoc-Phoi; Uettwiller, Florence; Melki, Isabelle; Mouy, Richard; Wouters, Carine; Bader-Meunier, Brigitte; Job-Deslandre, Chantal; Quartier, Pierre

2018-04-02

Childhood-onset spondyloarthropathies usually start with enthesitis and peripheral arthritis. However, axial disease may develop afterward. Patients are most often classified, following revised (Edmonton 2011) ILAR criteria, as enthesitis-related arthritis, psoriatic arthritis, or unclassified juvenile idiopathic arthritis, particularly in cases of psoriasis in the patient or a first-degree relative. In adults, peripheral spondyloarthritis is classified by ASAS criteria. We retrospectively studied patients with childhood-onset spondyloarthropathies followed for more than one year in our referral centre. We did not exclude patients with a personal or familial history of psoriasis. We included 114 patients followed between January 2008 and December 2015 for a median of 2.5 years (IQR = 2.3). Sixty-nine per-cent of patients fulfilled the revised ILAR classification criteria for enthesitis-related arthritis, and 92% the ASAS criteria for peripheral spondyolarthritis (p <  0.001). Axial disease and sacroiliitis were rare at disease onset. However, they appeared during follow-up in 63% and 47% of cases respectively, after a median disease duration of 2.6 (IC 95% [2.2-4.4]) and 5.3 years (IC 95% [4.1-7.7]), respectively. Multivariable analysis showed that familial history of spondyloarthritis was associated with the presence of sacroiliitis and active disease at the latest follow-up (OR = 3.61 [1.5-8.7], p <  0.01 and 2.98 [1.2-7.3], p = 0.02, respectively). Axial involvement developed in most patients within five years. Revised Edmonton criteria were less sensitive than ASAS criteria to classify patients as having childhood-onset spondyloarthropathies. The main risk factor for both sacroiliitis and persistent active disease was a familial history of spondyloarthritis.

The RAndomized Placebo Phase Study Of Rilonacept in the Treatment of Systemic Juvenile Idiopathic Arthritis (RAPPORT)

PubMed Central

Ilowite, Norman T.; Prather, Kristi; Lokhnygina, Yuliya; Schanberg, Laura E.; Elder, Melissa; Milojevic, Diana; Verbsky, James W.; Spalding, Steven J.; Kimura, Yukiko; Imundo, Lisa F.; Punaro, Marilynn G.; Sherry, David D.; Tarvin, Stacey E.; Zemel, Lawrence S.; Birmingham, James D.; Gottlieb, Beth S.; Miller, Michael L.; O'Neil, Kathleen; Ruth, Natasha M.; Wallace, Carol A.; Singer, Nora G.; Sandborg, Christy I.

2015-01-01

Background Interleukin-1 plays a pivotal role in in the pathogenesis of systemic juvenile idiopathic arthritis (sJIA). We assessed the efficacy and safety of rilonacept (IL-1 trap), an IL-1 inhibitor, in a randomized, double-blind, placebo-controlled trial. Methods An initial 4-week double-blind placebo phase was incorporated into a 24-week randomized multi-center design, followed by an open label phase. We randomized 71 children with at least 2 active joints 1:1 to 2 arms of the study. Patients in the rilonacept arm received rilonacept (4.4mg/kg loading dose followed by 2.2mg/kg weekly, subcutaneously) from day 0; patients in the placebo arm received placebo for 4 weeks followed by a loading dose of rilonacept at week 4 followed by weekly maintenance doses. The primary endpoint was time to response, using adapted JIA ACR30 response criteria coupled with absence of fever and taper of systemic corticosteroids using pre-specified criteria. Results Time to response was shorter in the rilonacept arm than in the placebo arm (Chi-square 7.235, P=.007). Secondary analysis showed 20/35 (57%) of patients in the rilonacept arm responded at week 4 compared to 9/33 (27%) in the placebo arm (P=.016) using the same response criteria. Exacerbation of sJIA (4) was the most common SAE. More patients in the rilonacept arm had elevated liver transaminases, including more than three times the upper limits of normal, as compared to those in the placebo arm. Adverse events were similar in the two arms of the study. Conclusions Rilonacept was generally well tolerated and demonstrated efficacy in active sJIA. PMID:24839206

Evidence for Tocilizumab as a Treatment Option in Refractory Uveitis Associated with Juvenile Idiopathic Arthritis.

PubMed

Tappeiner, Christoph; Mesquida, Marina; Adán, Alfredo; Anton, Jordi; Ramanan, Athimalaipet V; Carreno, Ester; Mackensen, Friederike; Kotaniemi, Kaisu; de Boer, Joke H; Bou, Rosa; de Vicuña, Carmen García; Heiligenhaus, Arnd

2016-12-01

To report on experience using the anti-interleukin 6 receptor antibody tocilizumab (TCZ) to treat severe and therapy-refractory uveitis associated with juvenile idiopathic arthritis (JIA). Retrospective data were gathered from patients with JIA receiving TCZ treatment for uveitis. JIA and related uveitis data (disease onset, activity, structural complications, and topical and systemic antiinflammatory treatment) were evaluated at the start of TCZ (baseline) and every 3 months during TCZ therapy. A total of 17 patients (14 women) with active uveitis were included (mean age 15.3 ± 6.9 yrs, mean followup time 8.5 mos). In all patients, uveitis had been refractory to previous topical and systemic corticosteroids, methotrexate (MTX), and other synthetic and biological disease-modifying antirheumatic drugs, including ≥ 1 tumor necrosis factor-α (TNF-α) inhibitor. Uveitis inactivity was achieved in 10 patients after a mean of 5.7 months of TCZ treatment (in 3 of them, it recurred during followup) and persisted in the remaining 7 patients. By using TCZ, systemic corticosteroids or immunosuppressives could be spared in 7 patients. Macular edema was present in 5 patients at baseline and improved in all of them under TCZ treatment. Arthritis was active in 11 patients at the initial and in 6 at the final followup visit. TCZ appears to represent a therapeutic option for severe JIA-associated uveitis that has been refractory to MTX and TNF-α inhibitors in selected patients. The present data indicate that inflammatory macular edema responds well to TCZ in patients with JIA-associated uveitis.

Race, ethnicity, and disease outcomes in juvenile idiopathic arthritis: a cross-sectional analysis of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry.

PubMed

Ringold, Sarah; Beukelman, Timothy; Nigrovic, Peter A; Kimura, Yukiko

2013-06-01

To measure the associations between self-reported race and ethnicity and disease outcomes, including joint damage, pain, and functional ability, in children with juvenile idiopathic arthritis (JIA). A cross-sectional analysis of children with JIA enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry between May 2010 and March 2012. Mann-Whitney U test and chi-square testing were used to compare patient characteristics between race (white, African American, or Asian) and ethnicity (Non-Hispanic and Non-Latino; Hispanic or Latino) categories. Logistic regression was used to measure the associations between each race or ethnicity category and the outcome of interest. Race category was available for 4292 of 4682 children (93% white, 5% African American, Asian 3%). Ethnicity data were available for 4644 (11% Hispanic or Latino). African American children with polyarticular-course JIA had an elevated OR for joint damage on radiographic imaging compared to white children (OR 1.9, 95% CI 1.0-3.1; p = 0.04). Hispanic/Latino children had increased odds of having disability scores > 75th percentile (OR 1.5, 95% CI 1.1-2.1; p < 0.01) compared to non-Hispanic/Latino children; however, these odds were no longer significant when the cohort was limited to children with polyarticular-course JIA. Asian children had decreased odds of higher pain and functional disability compared to white children (p < 0.05). Race and ethnicity were variably associated with joint damage, pain, and functional ability. Understanding outcome variation between different race and ethnicity groups may help to optimize care for children with JIA.

The pathogenesis of oligoarticular/polyarticular vs systemic juvenile idiopathic arthritis.

PubMed

Lin, Yu-Tsan; Wang, Chen-Ti; Gershwin, M Eric; Chiang, Bor-Luen

2011-06-01

Juvenile idiopathic arthritis (JIA) has had a long and difficult problem with classification. It is clearly a heterogeneous and multi-factorial autoimmune disease but all too often the distinctions among subtypes were unclear. In fact, there is now increasing evidence of a distinct pathogenesis of oligo/polyarticular JIA compared to systemic JIA. Oligo/polyarticular JIA is an antigen-driven lymphocyte-mediated autoimmune disease with abnormality in the adaptive immune system. Cartilage-derived auto-antigens activate autoreactive T cells including Th1 and Th17 cells with production of pro-inflammatory cytokines IFN-γ and IL-17. On the other hand, the inhibition of regulatory T (Treg) cells including natural Foxp3(+) Treg and self-heat shock protein-induced Treg cells with decreased anti-inflammatory cytokine IL-10 results in the loss of immune tolerance. Imbalance between autoreactive Th1/Th17 and Treg cells leads to the failure of T cell tolerance to self-antigens, which contributes to the synovial inflammation of oligo/polyarticular JIA. By contrast, systemic JIA is an autoinflammatory disease with abnormality in the innate immune system. A loss of control of the alternative secretory pathway leading to aberrant activation of phagocytes including monocytes, macrophages and neutrophils seems to be involved in the release of pro-inflammatory cytokines IL-1, IL-6, IL-18 and pro-inflammatory S100-proteins, which contribute to the multisystem inflammation of systemic JIA. Markedly distinct pathogenesis of oligo/polyarticular JIA and systemic JIA implies that they might need different treatment strategies. Copyright © 2011 Elsevier B.V. All rights reserved.

Investigation of type 1 diabetes and coeliac disease susceptibility loci for association with juvenile idiopathic arthritis.

PubMed

Hinks, Anne; Martin, Paul; Flynn, Edward; Eyre, Steve; Packham, Jon; Barton, Anne; Worthington, Jane; Thomson, Wendy

2010-12-01

There is strong evidence suggesting that juvenile idiopathic arthritis (JIA) shares many susceptibility loci with other autoimmune diseases. To investigate variants robustly associated with type 1 diabetes (T1D) or coeliac disease (CD) for association with JIA. Sixteen single-nucleotide polymorphisms (SNPs) already identified as susceptibility loci for T1D/CD were selected for genotyping in patients with JIA (n=1054) and healthy controls (n=3129). Genotype and allele frequencies were compared using the Cochrane-Armitage trend test implemented in PLINK. One SNP in the LPP gene, rs1464510, showed significant association with JIA (p(trend)=0.002, OR=1.18, 95% CI 1.06 to 1.30). A second SNP, rs653178 in ATXN2, also showed nominal evidence for association with JIA (p(trend)=0.02, OR=1.13, 95% CI 1.02 to 1.25). The SNP, rs17810546, in IL12A showed subtype-specific association with enthesitis-related arthritis (ERA) subtype (p(trend)=0.005, OR=1.88, 95% CI 1.2 to 2.94). Evidence for a novel JIA susceptibility locus, LPP, is presented. Association at the SH2B3/ATXN2 locus, previously reported to be associated with JIA in a US series, also supports this region as contributing to JIA susceptibility. In addition, a subtype-specific association of IL12A with ERA is identified. All findings will require validation in independent JIA cohorts.

Does intensive management improve remission rates in patients with intermediate rheumatoid arthritis? (the TITRATE trial): study protocol for a randomised controlled trial.

PubMed

Martin, Naomi H; Ibrahim, Fowzia; Tom, Brian; Galloway, James; Wailoo, Allan; Tosh, Jonathan; Lempp, Heidi; Prothero, Louise; Georgopoulou, Sofia; Sturt, Jackie; Scott, David L

2017-12-08

Uncontrolled active rheumatoid arthritis can lead to increasing disability and reduced quality of life over time. 'Treating to target' has been shown to be effective in active established disease and also in early disease. However, there is a lack of nationally agreed treatment protocols for patients with established rheumatoid arthritis who have intermediate disease activity. This trial is designed to investigate whether intensive management of disease leads to a greater number of remissions at 12 months. Levels of disability and quality of life, and acceptability and cost-effectiveness of the intervention will also be examined. The trial is a 12-month, pragmatic, randomised, open-label, two-arm, parallel-group, multicentre trial undertaken at specialist rheumatology centres across England. Three hundred and ninety-eight patients with established rheumatoid arthritis will be recruited. They will currently have intermediate disease activity (disease activity score for 28 joints assessed using an erythrocyte sedimentation rate of 3.2 to 5.1 with at least three active joints) and will be taking at least one disease-modifying anti-rheumatic drug. Participants will be randomly selected to receive intensive management or standard care. Intensive management will involve monthly clinical reviews with a specialist health practitioner, where drug treatment will be optimised and an individualised treatment support programme delivered based on several principles of motivational interviewing to address identified problem areas, such as pain, fatigue and adherence. Standard care will follow standard local pathways and will be in line with current English guidelines from the National Institute for Health and Clinical Excellence. Patients will be assessed initially and at 6 and 12 months through self-completed questionnaires and clinical evaluation. The trial will establish whether the known benefits of intensive treatment strategies in active rheumatoid arthritis are also seen

HLA-B27 subtypes in enthesitis-related arthritis category of juvenile idiopathic arthritis and ankylosing spondylitis in northern India.

PubMed

Srivastava, R; Agnihotry, S; Aggarwal, R; Bajpai, P; Aggarwal, A

2015-01-01

Enthesitis-related arthritis (ERA) is the most common form of juvenile idiopathic arthritis (JIA) in the Asian and Indian populations. The presence of HLA-B27 has a strong association with JIA-ERA similar to that with adult ankylosing spondylitis (AS). The HLA-B27gene is highly polymorphic. Susceptibility to AS varies between different HLA-B27 subtypes; data on the relationship of susceptibility to JIA-ERA with HLA-B27 types are scant. In this study, we determined HLA-B27 subtypes in patients with JIA-ERA and AS to find out whether there is any difference in the HLA-B27 subtypes prevalent in these two diseases. Genomic DNA from 135 patients with JIA-ERA and 121 with AS was tested for the presence of HLA-B27. In patients testing positive, HLA-B27subtyping was done by sequencing a genomic region that contained second and third exons and the intervening intron of this gene; this method permitted identification of common HLA-B27 subtypes (HLA-B*27:01 to HLA-B*27:09). One hundred and seven (79%) patients with JIA-ERA and 102 (84%) patients with AS tested positive for HLA-B27. In both groups, HLA-B*27:05 and HLA-B*27:04 were the common subtypes; some patients had HLA-B*27:07(7.4%) and HLA-B*27:18. Patients with JIA-ERA had a higher frequency of HLA-B*27:05 than those with AS (70% vs. 57%, p=0.047), and a lower frequency of HLA-B*27:04 (21% vs. 36%, p=0.018). HLA-B*27:05 and HLA-B*27:04 were the most common HLA-27 subtypes in both JIA-ERA and AS. However, HLA-B*27:05 was more frequent and HLA-B*27:04 was less frequent in JIA-ERA. It is possible that HLA-B*27:05 being the ancestral HLA-27 subtype leads to expression of disease early in life.

Emotion Regulation Predicts Pain and Functioning in Children With Juvenile Idiopathic Arthritis: An Electronic Diary Study

PubMed Central

Bromberg, Maggie H.; Anthony, Kelly K.; Gil, Karen M.; Franks, Lindsey; Schanberg, Laura E.

2012-01-01

Objectives This study utilized e-diaries to evaluate whether components of emotion regulation predict daily pain and function in children with juvenile idiopathic arthritis (JIA). Methods 43 children ages 8–17 years and their caregivers provided baseline reports of child emotion regulation. Children then completed thrice daily e-diary assessments of emotion, pain, and activity involvement for 28 days. E-diary ratings of negative and positive emotions were used to calculate emotion variability and to infer adaptive emotion modulation following periods of high or low emotion intensity. Hierarchical linear models were used to evaluate how emotion regulation related to pain and function. Results The attenuation of negative emotion following a period of high negative emotion predicted reduced pain; greater variability of negative emotion predicted higher pain and increased activity limitation. Indices of positive emotion regulation also significantly predicted pain. Conclusions Components of emotion regulation as captured by e-diaries predict important health outcomes in children with JIA. PMID:22037006

Intravenous immunoglobulin therapy leading to dramatic improvement in a patient with systemic juvenile idiopathic arthritis and severe pericarditis resistant to steroid pulse therapy.

PubMed

Aizawa-Yashiro, Tomomi; Oki, Eishin; Tsuruga, Kazushi; Nakahata, Tohru; Ito, Etsuro; Tanaka, Hiroshi

2012-05-01

A 7-year-old Japanese boy with a 4-month history of systemic juvenile idiopathic arthritis (s-JIA) experienced disease flare with spiking fever, exanthema and arthralgia. He then developed progressive dyspnea due to severe pericarditis, and proinflammatory hypercytokinemia was suspected. Methylprednisolone pulse therapy was ineffective and echocardiography showed massive pericardial effusion had persisted. Alternatively, subsequent intravenous immunoglobulin (IVIG) therapy resulted in dramatic resolution of the pericardial effusion, and his general condition significantly improved within a few days. This case report may lend further support the use of IVIG for selected patients with s-JIA and severe pericarditis.

Infrapatellar bursitis in children with juvenile idiopathic arthritis: a case series.

PubMed

Alqanatish, Jubran T; Petty, Ross E; Houghton, Kristin M; Guzman, Jaime; Tucker, Lori B; Cabral, David A; Cairns, Robyn A

2011-02-01

Children with juvenile idiopathic arthritis (JIA) may infrequently present with localized anterior knee pain or swelling, in addition to generalize knee pain induced by JIA. We report five cases of deep infrapatellar bursitis in children with JIA. The clinical features, radiological findings, management, and outcome of five children with JIA and deep infrapatellar bursitis are reviewed. Three boys and two girls with a mean age of 9.8 years (range 6-14 years) were reviewed. Four children had persistent oligoarticular JIA, and one child had extended oligoarticular JIA. The presentation of deep infrapatellar bursitis was variable. In only one patient was the bursal swelling painful. Knee magnetic resonance imaging (MRI) was performed in four patients and demonstrated coexistent knee joint synovitis in three. Treatment included targeted corticosteroid injections into the deep infrapatellar bursa in two cases with complete resolution. One case was treated with corticosteroid injection by an outside health care provider with poor clinical response. Two cases are being treated with non-steroidal anti-inflammatory drugs and methotrexate. Deep infrapatellar bursitis can occur as an isolated finding or concurrently with knee joint synovitis in patients with JIA. Awareness of this entity is important because direct injection of the bursa may be needed for treatment, as the bursa does not communicate with the knee joint. Furthermore, when bursitis is suspected in JIA, MRI can be helpful to confirm the diagnosis, detect concurrent knee joint synovitis, and exclude other pathologies.

Promoting physical activity in children with juvenile idiopathic arthritis through an internet-based program: results of a pilot randomized controlled trial.

PubMed

Lelieveld, Otto T H M; Armbrust, Wineke; Geertzen, Jan H B; de Graaf, Inez; van Leeuwen, Miek A; Sauer, Pieter J J; van Weert, Ellen; Bouma, Jelte

2010-05-01

Patients with juvenile idiopathic arthritis (JIA) are less physically active than healthy peers. Therefore, we developed an Internet-based intervention to improve physical activity (PA). The aim of this study was to examine the effectiveness of the program in improving PA. PA was determined by activity-related energy expenditure, PA level, time spent on moderate to vigorous PA, and the number of days with > or =1 hour of moderate to vigorous activity, and was assessed with a 7-day activity diary. Aerobic exercise capacity was assessed by means of a Bruce treadmill test and was recorded as maximum endurance time. Disease activity was assessed by using the JIA core set. Adherence was electronically monitored. Of 59 patients, 33 eligible patients were included and randomized in an intervention (n = 17, mean +/- SD age 10.6 +/- 1.5 years) or control waiting-list group (n = 16, mean +/- SD age 10.8 +/- 1.4 years). All patients completed baseline and T1 testing. PA significantly improved in both groups. Maximum endurance time significantly improved in the intervention group but not in the control group. In a subgroup analysis for patients with low PA (intervention: n = 7, control: n = 5), PA improved in the intervention group but not in the control group. The intervention was safe, feasible, and showed a good adherence. An Internet-based program for children with JIA ages 8-12 years directed at promoting PA in daily life effectively improves PA in those patients with low PA levels. It is also able to improve endurance and it is safe, feasible, and has good adherence.

An exploration of parents' preferences for foot care in juvenile idiopathic arthritis: a possible role for the discrete choice experiment.

PubMed

Hendry, Gordon J; Turner, Debbie E; Gardner-Medwin, Janet; Lorgelly, Paula K; Woodburn, James

2014-02-06

An increased awareness of patients' and parents' care preferences regarding foot care is desirable from a clinical perspective as such information may be utilised to optimise care delivery. The aim of this study was to examine parents' preferences for, and valuations of foot care and foot-related outcomes in juvenile idiopathic arthritis (JIA). A discrete choice experiment (DCE) incorporating willingness-to-pay (WTP) questions was conducted by surveying 42 parents of children with JIA who were enrolled in a randomised-controlled trial of multidisciplinary foot care at a single UK paediatric rheumatology outpatients department. Attributes explored were: levels of pain; mobility; ability to perform activities of daily living (ADL); waiting time; referral route; and footwear. The DCE was administered at trial baseline. DCE data were analysed using a multinomial-logit-regression model to estimate preferences and relative importance of attributes of foot care. A stated-preference WTP question was presented to estimate parents' monetary valuation of health and service improvements. Every attribute in the DCE was statistically significant (p < 0.01) except that of cost (p = 0.118), suggesting that all attributes, except cost, have an impact on parents' preferences for foot care for their child. The magnitudes of the coefficients indicate that the strength of preference for each attribute was (in descending order): improved ability to perform ADL, reductions in foot pain, improved mobility, improved ability to wear desired footwear, multidisciplinary foot care route, and reduced waiting time. Parents' estimated mean annual WTP for a multidisciplinary foot care service was £1,119.05. In terms of foot care service provision for children with JIA, parents appear to prefer improvements in health outcomes over non-health outcomes and service process attributes. Cost was relatively less important than other attributes suggesting that it does not appear to impact on

An exploration of parents’ preferences for foot care in juvenile idiopathic arthritis: a possible role for the discrete choice experiment

PubMed Central

2014-01-01

Background An increased awareness of patients’ and parents’ care preferences regarding foot care is desirable from a clinical perspective as such information may be utilised to optimise care delivery. The aim of this study was to examine parents’ preferences for, and valuations of foot care and foot-related outcomes in juvenile idiopathic arthritis (JIA). Methods A discrete choice experiment (DCE) incorporating willingness-to-pay (WTP) questions was conducted by surveying 42 parents of children with JIA who were enrolled in a randomised-controlled trial of multidisciplinary foot care at a single UK paediatric rheumatology outpatients department. Attributes explored were: levels of pain; mobility; ability to perform activities of daily living (ADL); waiting time; referral route; and footwear. The DCE was administered at trial baseline. DCE data were analysed using a multinomial-logit-regression model to estimate preferences and relative importance of attributes of foot care. A stated-preference WTP question was presented to estimate parents’ monetary valuation of health and service improvements. Results Every attribute in the DCE was statistically significant (p < 0.01) except that of cost (p = 0.118), suggesting that all attributes, except cost, have an impact on parents’ preferences for foot care for their child. The magnitudes of the coefficients indicate that the strength of preference for each attribute was (in descending order): improved ability to perform ADL, reductions in foot pain, improved mobility, improved ability to wear desired footwear, multidisciplinary foot care route, and reduced waiting time. Parents’ estimated mean annual WTP for a multidisciplinary foot care service was £1,119.05. Conclusions In terms of foot care service provision for children with JIA, parents appear to prefer improvements in health outcomes over non-health outcomes and service process attributes. Cost was relatively less important than other attributes

Influence of etanercept on leptin and ghrelin secretion in children with juvenile idiopathic arthritis

PubMed Central

Maciejewska-Paszek, Izabela; Grochowska-Niedworok, Elżbieta; Siwiec, Andrzej; Gruenpeter, Anna; Dul, Lechosław

2017-01-01

Objective To assess possible changes in leptin and ghrelin secretion due to etanercept in juvenile idiopathic arthritis (JIA). Methods 50 patients with JIA and 16 age-matched controls were enrolled into this prospective, cross-sectional study. Serum leptin, total and acyl ghrelin were measured in addition to white blood cell (WBC) and lymphocyte counts. Results 25 patients received etanercept and 25 conventional therapies (including methotrexate) for JIA. There was no difference between treatment and control groups in leptin or ghrelin levels and no evidence of a relationship between leptin and ghrelin in patients with JIA. In all children with JIA there was a correlation between leptin and body mass index (BMI). However, compared with children in the conventional treatment group, children in the etanercept group showed a positive correlation between total ghrelin and BMI and those with a low BMI showed a negative correlation between acyl ghrelin and BMI. Conclusion No differences in leptin and ghrelin concentrations were found when patients with JIA and controls were compared or when patients who received etanercept were compared with those who received conventional treatment for JIA. PMID:28415953

Effects of Pilates exercises on health-related quality of life in individuals with juvenile idiopathic arthritis.

PubMed

Mendonça, Tânia M; Terreri, Maria T; Silva, Carlos H; Neto, Morun Bernardino; Pinto, Rogério M; Natour, Jamil; Len, Claudio A

2013-11-01

To determine the effects of Pilates exercises on health-related quality of life (HRQOL) in individuals with juvenile idiopathic arthritis (JIA). Randomized, prospective, single-blind trial. Outpatient clinic of pediatric rheumatology and the rehabilitation department. Children (N=50) with JIA according to the International League of Associations for Rheumatology criteria. Participants were randomly assigned into 2 groups. In group I (n=25), the participants were given a conventional exercise program for 6 months. Patients in group II (n=25) participated in a Pilates exercise program for 6 months. The primary outcome measure was HRQOL, as measured by the Pediatric Quality of Life Inventory version 4.0 (PedsQL 4.0). The secondary outcome measures provided an estimate of the clinical relevance of the primary outcome results and included joint pain intensity (according to a 10-cm visual analog scale), disability (according to the Childhood Health Assessment Questionnaire), joint status (using the Pediatric Escola Paulista de Medicina Range of Motion Scale), and the total PedsQL 4.0 score. All participants completed the study. The scores of the PedsQL 4.0 differed significantly between groups, indicating that Pilates exercises increased these scores when compared with the conventional exercise program. Group II participants showed significant improvements in the 10-cm visual analog scale-joint pain, Childhood Health Assessment Questionnaire, and Pediatric Escola Paulista de Medicina Range of Motion Scale. The use of Pilates exercises had a positive physical and psychosocial impact on HRQOL in individuals with JIA. Future multicenter studies with a follow-up beyond the period of treatment using more objective parameters will be useful to support the results of the present study. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Imaging in juvenile idiopathic arthritis with a focus on ultrasonography.

PubMed

Laurell, Louise; Court-Payen, Michel; Boesen, Mikael; Fasth, Anders

2013-01-01

Early therapeutic intervention and use of new highly efficacious treatments have improved the outcome in many patients with juvenile idiopathic arthritis (JIA), but have also led to the need for more precise methods to evaluate disease activity. In adult rheumatology, numerous studies have established the importance of magnetic resonance imaging (MRI) and ultrasonography (US), and MRI is considered the reference standard. Nevertheless, due to differences in disease characteristics and the unique features of the growing skeleton, the findings obtained in adults are not directly applicable to children and adolescents. For paediatric patients, US offers specific advantages over MRI, because it is non-invasive, does not require sedation or general anesthesia (which facilitates repeated examinations for follow-up), is quickly accessible bedside, and is easy to combine with clinical assessment (interactivity). Agitation of the patient is rarely a problem, and hence young children can be seated on a parent's lap or play while being examined, and multiple locations can be assessed during a single session. Furthermore, modern high-frequency US transducers used by experienced US examiners can provide unsurpassed resolution of the superficial musculoskeletal structures in children. US is also the best available technique for imaging guidance of steroid injections. Unfortunately, there are still no validated MRI or US scoring systems for evaluating inflammatory and joint damage abnormalities in JIA, and few US studies have been conducted. Sonographic assessment of disease activity has, however, been proven to be more informative than clinical examination and is also readily available at points of care. This review summarises the literature on imaging in JIA, focusing on US and the important role this technique will play in JIA in the future.

Intra-articular radioactive yttrium and triamcinolone hexacetonide: an inconclusive trial. Arthritis and Rheumatism Council Multicentre Radiosynoviorthesis Trial Group.

PubMed

1984-08-01

A restricted sequential design multicentre controlled trial of yttrium-90 against triamcinolone intra-articularly was undertaken in patients with rheumatoid arthritis with knee involvement. The trial had to be discontinued because of dwindling recruitment over time. The reasons for this and other features contributing to an inconclusive outcome are noted. This experience lends little encouragement to the idea that yttrium-90 therapy is more or less advantageous than triamcinolone hexacetonide.

Juvenile idiopathic arthritis in adulthood: fulfilment of classification criteria for adult rheumatic diseases, long-term outcomes and predictors of inactive disease, functional status and damage.

PubMed

Oliveira-Ramos, Filipa; Eusébio, Mónica; M Martins, Fernando; Mourão, Ana Filipa; Furtado, Carolina; Campanilho-Marques, Raquel; Cordeiro, Inês; Ferreira, Joana; Cerqueira, Marcos; Figueira, Ricardo; Brito, Iva; Canhão, Helena; Santos, Maria José; Melo-Gomes, José A; Fonseca, João Eurico

2016-01-01

To determine how adult juvenile idiopathic arthritis (JIA) patients fulfil classification criteria for adult rheumatic diseases, evaluate their outcomes and determine clinical predictors of inactive disease, functional status and damage. Patients with JIA registered on the Rheumatic Diseases Portuguese Register (Reuma.pt) older than 18 years and with more than 5 years of disease duration were included. Data regarding sociodemographic features, fulfilment of adult classification criteria, Health Assessment Questionnaire, Juvenile Arthritis Damage Index-articular (JADI-A) and Juvenile Arthritis Damage Index-extra-articular (JADI-E) damage index and disease activity were analysed. 426 patients were included. Most of patients with systemic JIA fulfilled criteria for Adult Still's disease. 95.6% of the patients with rheumatoid factor (RF)-positive polyarthritis and 57.1% of the patients with RF-negative polyarthritis matched criteria for rheumatoid arthritis (RA). 38.9% of the patients with extended oligoarthritis were classified as RA while 34.8% of the patients with persistent oligoarthritis were classified as spondyloarthritis. Patients with enthesitis-related arthritis fulfilled criteria for spondyloarthritis in 94.7%. Patients with psoriatic arthritis maintained this classification. Patients with inactive disease had lower disease duration, lower diagnosis delay and corticosteroids exposure. Longer disease duration was associated with higher HAQ, JADI-A and JADI-E. Higher JADI-A was also associated with biological treatment and retirement due to JIA disability and higher JADI-E with corticosteroids exposure. Younger age at disease onset was predictive of higher HAQ, JADI-A and JADI-E and decreased the chance of inactive disease. Most of the included patients fulfilled classification criteria for adult rheumatic diseases, maintain active disease and have functional impairment. Younger age at disease onset was predictive of higher disability and decreased the

Harnessing interactive technologies to improve health outcomes in juvenile idiopathic arthritis.

PubMed

Coda, Andrea; Sculley, Dean; Santos, Derek; Girones, Xavier; Brosseau, Lucie; Smith, Derek R; Burns, Joshua; Rome, Keith; Munro, Jane; Singh-Grewal, Davinder

2017-05-16

Children and adolescents with Juvenile Idiopathic Arthritis (JIA) typically have reduced physical activity level and impaired aerobic and anaerobic exercise capacity when compared to their non-JIA counterparts. Low intensity exercise regimens appear to be safe in children with JIA and may results in improvements in overall physical function. Poor adherence to paediatric rheumatology treatment may lead to negative clinical outcomes and possibly increased disease activity. This includes symptoms such as pain, fatigue, quality of life, longer term outcomes including joint damage, as well as increase of healthcare associated costs. Low adherence to medications such as methotrexate and biological-drugs remains a significant issue for paediatric rheumatologists, with alarming reports that less than half of the children with JIA are compliant to drug-therapy. The recent advances in interactive technology resulting in a variety of wearable user-friendly smart devices may become a key solution to address important questions in JIA clinical management. Fully understanding the impact that arthritis and treatment complications have upon individual children and their families has long been a challenge for clinicians. Modern interactive technologies can be customised and accessed directly in the hands or wrists of children with JIA. These secured networks could be accessible 'live' at anytime and anywhere by the child, parents and clinicians. Multidisciplinary teams in paediatric rheumatology may benefit from adopting these technologies to better understand domains such as patient biological parameters, symptoms progression, adherence to drug-therapy, quality of life, and participation in physical activities. Most importantly the use of smart devices technologies may also facilitate more timely clinical decisions, improve self-management and parents awareness in the progression of their child's disease. Paediatric rheumatology research could also benefit from the use of these

Relapse rate of uveitis post-methotrexate treatment in juvenile idiopathic arthritis.

PubMed

Kalinina Ayuso, Viera; van de Winkel, Evelyne Leonce; Rothova, Aniki; de Boer, Joke Helena

2011-02-01

To evaluate the efficacy of methotrexate (MTX) and the effect of its withdrawal on relapse rate of uveitis associated with juvenile idiopathic arthritis (JIA). Retrospective case series. Data of 22 pediatric JIA patients who were being treated with MTX for active uveitis were studied retrospectively. Relapse rate after the withdrawal of MTX was established. Anterior chamber (AC) inflammation, topical steroid use during the first year of MTX treatment, and associations of relapses after the withdrawal were evaluated statistically. Duration of MTX treatment and its withdrawal was determined individually in collaboration with a rheumatologist with an intention to continue the treatment for at least 1 year and to withdraw in case of inactivity of uveitis and arthritis. Inactivity of uveitis was defined as the presence of ≤0.5+ cells in the AC. Eighteen patients (18/22; 82%) showed improvement of their uveitis with a significant decrease in activity of AC inflammation after a minimal period of 3 months of MTX treatment. A topical steroid-sparing effect was observed when MTX was administered for a period of 3 to 9 months. MTX was discontinued because of inactive uveitis in 13 patients. In 9 patients (8/13; 69%) a relapse of uveitis was observed after a mean time of 7.5 months (± SD 7.3). Six patients (6/13; 46%) had a relapse within the first year after the withdrawal. Relapse-free survival after withdrawal of MTX was significantly longer in patients who had been treated with MTX for more than 3 years (P = .009), children who were older than 8 years at the moment of withdrawal (P = .003), and patients who had an inactivity of uveitis of longer than 2 years before withdrawal of MTX (P = .033). Longer inactivity under MTX therapy was independently protective for relapses after the withdrawal (hazard ratio = 0.07; 95% confidence interval 0.01-0.86; P = .038), which means that 1-year increase of duration of inactive uveitis before the withdrawal of MTX results in a

Intra-articular radioactive yttrium and triamcinolone hexacetonide: an inconclusive trial. Arthritis and Rheumatism Council Multicentre Radiosynoviorthesis Trial Group.

PubMed Central

1984-01-01

A restricted sequential design multicentre controlled trial of yttrium-90 against triamcinolone intra-articularly was undertaken in patients with rheumatoid arthritis with knee involvement. The trial had to be discontinued because of dwindling recruitment over time. The reasons for this and other features contributing to an inconclusive outcome are noted. This experience lends little encouragement to the idea that yttrium-90 therapy is more or less advantageous than triamcinolone hexacetonide. PMID:6383234

Idiopathic hypersomnia.

PubMed

Billiard, Michel; Sonka, Karel

2016-10-01

Idiopathic hypersomnia continues to evolve from the concept of "sleep drunkenness" introduced by Bedrich Roth in Prague in 1956 and the description of idiopathic hypersomnia with two forms, polysymptomatic and monosymptomatic, by the same Bedrich Roth in 1976. The diagnostic criteria of idiopathic hypersomnia have varied with the successive revisions of the International classifications of sleep disorders, including the recent 3rd edition. No epidemiological studies have been conducted so far. Disease onset occurs most often during adolescence or young adulthood. A familial background is often present but rigorous studies are still lacking. The key manifestation is hypersomnolence. It is often accompanied by sleep of long duration and debilitating sleep inertia. Polysomnography (PSG) followed by a multiple sleep latency test (MSLT) is mandatory, as well as a 24 h PSG or a 2-wk actigraphy in association with a sleep log to ensure a total 24-h sleep time longer than or equal to 66O minutes, when the mean sleep latency on the MSLT is longer than 8 min. Yet, MSLT is neither sensitive nor specific and the polysomnographic diagnostic criteria require continuous readjustment and biologic markers are still lacking. Idiopathic hypersomnia is most often a chronic condition though spontaneous remission may occur. The condition is disabling, sometimes even more so than narcolepsy type 1 or 2. Based on neurochemical, genetic and immunological analyses as well as on exploration of the homeostatic and circadian processes of sleep, various pathophysiological hypotheses have been proposed. Differential diagnosis involves a number of diseases and it is not yet clear whether idiopathic hypersomnia and narcolepsy type 2 are not the same condition. Until now, the treatment of idiopathic hypersomnia has mirrored that of the sleepiness of narcolepsy type 1 or 2. The first randomized, double-blind, placebo-controlled trials of modafinil have just been published, as well as a double

The idiopathic intracranial hypertension treatment trial: clinical profile at baseline.

PubMed

Wall, Michael; Kupersmith, Mark J; Kieburtz, Karl D; Corbett, James J; Feldon, Steven E; Friedman, Deborah I; Katz, David M; Keltner, John L; Schron, Eleanor B; McDermott, Michael P

2014-06-01

To our knowledge, there are no large prospective cohorts of untreated patients with idiopathic intracranial hypertension (IIH) to characterize the disease. To report the baseline clinical and laboratory features of patients enrolled in the Idiopathic Intracranial Hypertension Treatment Trial. We collected data at baseline from questionnaires, examinations, automated perimetry, and fundus photography grading. Patients (n = 165) were enrolled from March 17, 2010, to November 27, 2012, at 38 academic and private practice sites in North America. All participants met the modified Dandy criteria for IIH and had a perimetric mean deviation between -2 dB and -7 dB. All but 4 participants were women. Baseline and laboratory characteristics. The mean (SD) age of our patients was 29.0 (7.4) years and 4 (2.4%) were men. The average (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 39.9 (8.3). Headache was the most common symptom (84%). Transient visual obscurations occurred in 68% of patients, back pain in 53%, and pulse synchronous tinnitus in 52%. Only 32% reported visual loss. The average (SD) perimetric mean deviation in the worst eye was -3.5 (1.1) dB, (range, -2.0 to -6.4 dB) and in the best eye was -2.3 (1.1) dB (range, -5.2 to 0.8 dB). A partial arcuate visual field defect with an enlarged blind spot was the most common perimetric finding. Visual acuity was 85 letters or better (20/20) in 71% of the worst eyes and 77% of the best eyes. Quality of life measures, including the National Eye Institute Visual Function Questionnaire-25 and the Short Form-36 physical and mental health summary scales, were lower compared with population norms. The Idiopathic Intracranial Hypertension Treatment Trial represents the largest prospectively analyzed cohort of untreated patients with IIH. Our data show that IIH is almost exclusively a disease of obese young women. Patients with IIH with mild visual loss have typical symptoms, may

Short term effectiveness and experiences of a peer guided web-based self-management intervention for young adults with juvenile idiopathic arthritis.

PubMed

Ammerlaan, Judy; van Os-Medendorp, Harmieke; de Boer-Nijhof, Nienke; Scholtus, Lieske; Kruize, Aike A; van Pelt, Philomine; Prakken, Berent; Bijlsma, Hans

2017-10-13

A web-based self-management intervention guided by peer-trainers was developed to support young adults' self-management in coping with Juvenile Idiopathic Arthritis (JIA). To investigate its effectiveness, a randomized controlled trial (RCT) was conducted. In addition, the content of the chat and participants' goals were studied to identify underlying processes. An RCT with a six-month follow up period was conducted among 72 young adults with JIA, aged between 16 and 25 years old, randomly assigned to the intervention or to the usual care control group. After 24 weeks, in both groups 24 participants completed all measurements. Intentions to treat analyses were carried out by means of linear mixed models for longitudinal measurements. With self-efficacy as primary outcome, self-management, disease activity, quality of life, absenteeism of school/work, health care medication use and adherence to the intervention were studied. The participants' goals, personal achievements, interactions on the chat, and their appreciation of the intervention were analyzed using thematic analyses. No significant differences were found on self-efficacy, quality of life, and self-management between the participants of the control group and the intervention group. In the intervention group, modeling and sharing experiences were the most recognized themes. Fifty-five goals were formulated and divided into the following categories: improvement and maintaining balance, setting and recognizing boundaries, communicating and coping with incomprehension. Adherence, appreciation of the own learning experience, and personal achievements were rated positively. The web-based intervention did not lead to an improvement of self-efficacy. However, additional qualitative analyses showed that the intervention was appreciated and valuable for the participants. More research is needed on how to measure the added value of this intervention compared to the usual care. Trial registration number NTR4679 .

The effectiveness of core stabilization exercise in adolescent idiopathic scoliosis: A randomized controlled trial.

PubMed

Gür, Gözde; Ayhan, Cigdem; Yakut, Yavuz

2017-06-01

Core stabilization training is used to improve postural balance in musculoskeletal problems. The purpose of this study was to investigate the effectiveness of stabilization training in adolescent idiopathic scoliosis. A randomized controlled trial, pretest-posttest design. In total, 25 subjects with adolescent idiopathic scoliosis were randomly divided into two groups: stabilization group ( n = 12) and control group ( n = 13). The stabilization group received core stabilization in addition to traditional rehabilitation, and the control group received traditional rehabilitation for 10 weeks. Assessment included Cobb's angle on radiograph, apical vertebral rotation in Adam's test, trunk asymmetry (Posterior Trunk Symmetry Index), cosmetic trunk deformity (Trunk Appearance Perception Scale), and quality of life (Scoliosis Research Society-22 questionnaire). Inter-group comparisons showed significantly greater improvements in the mean change in lumbar apical vertebral rotation degree and the pain domain of Scoliosis Research Society-22 in the stabilization group than those in the control group ( p < 0.05). No significant differences were observed for other measurements between the groups; however, trends toward greater improvement were observed in the stabilization group. Core stabilization training in addition to traditional exercises was more effective than traditional exercises alone in the correction of vertebral rotation and reduction of pain in adolescent idiopathic scoliosis. Clinical relevance Stabilization exercises are more effective in reducing rotation deformity and pain than traditional exercises in the conservative rehabilitation of adolescent idiopathic scoliosis. These improvements suggest that stabilization training should be added to rehabilitation programs in adolescent idiopathic scoliosis.

Distinct expression pattern of IFN-alpha and TNF-alpha in juvenile idiopathic arthritis synovial tissue.

PubMed

Gattorno, M; Chicha, L; Gregorio, A; Ferlito, F; Rossi, F; Jarrossay, D; Lanzavecchia, A; Martini, A; Manz, M G

2007-04-01

Recent laboratory and clinical data suggest that two prototype autoimmune diseases, systemic lupus erythematosus and rheumatoid arthritis are mainly driven by distinct cytokines, interferon (IFN)-alpha and tumour necrosis factor (TNF)-alpha, respectively. We here investigated the presence and characteristics of natural type I IFN-producing cells (IPCs), as well as IFN-alpha and TNF-alpha expression at sites of inflammation in juvenile idiopathic arthritis (JIA). Peripheral blood (PB) and synovial fluid (SF) mononuclear cells (MNCs) (n = 25 each) from JIA patients with active disease were studied. IPCs were identified as BCDA-2(+)CD123(+)HLA-DR(+)CD45RA(+) cells, and dendritic cells (DCs) as CD11c(+)CD14(-/low)lin(-) cells by flow cytometry. IPCs and DCs were analysed for Toll-like receptor-7 and -9 mRNA expression by real-time polymerase chain reaction. IFN-alpha was measured by enzyme-linked immunosorbent assay in serum, SF and in supernatants of influenza virus-infected, cultured IPCs. Synovial tissues of n = 6 additional JIA patients were analysed by immunohistochemistry using mAbs against CD123, IFN-alpha, TNF-alpha, CD3, CD19 and CD138. IPCs were enriched in SF MNCs compared with PB MNCs in all JIA patients. Influenza-induced, but no spontaneous IFN-alpha release was detected from SF IPCs, and serum and SF IFN-alpha levels were not elevated. Nonetheless, in synovial tissue IFN-alpha producing cells accumulated at inflammatory lymph-follicular-like structures, while TNF-alpha producing cells were mostly found at the lining and sublining layers. These data suggest that besides TNF-alpha-expressing cells, IFN-alpha-producing IPCs are involved in initiation, maintenance or regulation of the inflammatory response in JIA.

Association of HLA-A*02:06 and HLA-DRB1*04:05 with clinical subtypes of juvenile idiopathic arthritis.

PubMed

Yanagimachi, Masakatsu; Miyamae, Takako; Naruto, Takuya; Hara, Takuma; Kikuchi, Masako; Hara, Ryoki; Imagawa, Tomoyuki; Mori, Masaaki; Kaneko, Tetsuji; Goto, Hiroaki; Morita, Satoshi; Mizuki, Nobuhisa; Kimura, Akinori; Yokota, Shumpei

2011-03-01

Juvenile idiopathic arthritis (JIA) is one of the most common forms of pediatric chronic arthritis. JIA is a clinically heterogeneous disease. Therefore, the genetic background of JIA may also be heterogeneous. The aim of this study was to investigate associations between human leukocyte antigen (HLA) and susceptibility to JIA and/or uveitis, which is one of the most devastating complications of JIA. A total of 106 Japanese articular JIA patients (67 with polyarthritis and 39 with oligoarthritis) and 678 healthy controls were genotyped for HLA-A, -B and -DRB1 by PCR-sequence-specific oligonucleotide probe methodology. HLA-A(*)02:06 was the risk factor for JIA accompanied by uveitis after adjustment for clinical factors (corrected P-value < 0.001, odds ratio (OR) 11.7, 95% confidence interval (CI) 3.2-43.0). On the other hand, HLA-DRB1(*)04:05 was associated with polyarticular JIA (corrected P-value < 0.001, OR 2.9, 95% CI 1.7-4.8). We found an association of HLA-A(*)02:06 with susceptibility to JIA accompanied by uveitis, which might be considered a separate clinical JIA entity. We also found an association between HLA-DRB1(*)04:05 and polyarticular JIA. Thus, clinical subtypes of JIA can be classified by the presence of the specific HLA alleles, HLA-A(*)02:06 and DRB1(*)04:05.

Growth and weight gain in children with juvenile idiopathic arthritis: results from the ReACCh-Out cohort.

PubMed

Guzman, Jaime; Kerr, Tristan; Ward, Leanne M; Ma, Jinhui; Oen, Kiem; Rosenberg, Alan M; Feldman, Brian M; Boire, Gilles; Houghton, Kristin; Dancey, Paul; Scuccimarri, Rosie; Bruns, Alessandra; Huber, Adam M; Watanabe Duffy, Karen; Shiff, Natalie J; Berard, Roberta A; Levy, Deborah M; Stringer, Elizabeth; Morishita, Kimberly; Johnson, Nicole; Cabral, David A; Larché, Maggie; Petty, Ross E; Laxer, Ronald M; Silverman, Earl; Miettunen, Paivi; Chetaille, Anne-Laure; Haddad, Elie; Spiegel, Lynn; Turvey, Stuart E; Schmeling, Heinrike; Lang, Bianca; Ellsworth, Janet; Ramsey, Suzanne E; Roth, Johannes; Campillo, Sarah; Benseler, Susanne; Chédeville, Gaëlle; Schneider, Rayfel; Tse, Shirley M L; Bolaria, Roxana; Gross, Katherine; Feldman, Debbie; Cameron, Bonnie; Jurencak, Roman; Dorval, Jean; LeBlanc, Claire; St Cyr, Claire; Gibbon, Michele; Yeung, Rae S M; Duffy, Ciarán M; Tucker, Lori B

2017-08-22

With modern treatments, the effect of juvenile idiopathic arthritis (JIA) on growth may be less than previously reported. Our objective was to describe height, weight and body mass index (BMI) development in a contemporary JIA inception cohort. Canadian children newly-diagnosed with JIA 2005-2010 had weight and height measurements every 6 months for 2 years, then yearly up to 5 years. These measurements were used to calculate mean age- and sex-standardized Z-scores, and estimate prevalence and cumulative incidence of growth impairments, and the impact of disease activity and corticosteroids on growth. One thousand one hundred forty seven children were followed for median 35.5 months. Mean Z-scores, and the point prevalence of short stature (height < 2.5th percentile, 2.5% to 3.4%) and obesity (BMI > 95th percentile, 15.8% to 16.4%) remained unchanged in the whole cohort. Thirty-three children (2.9%) developed new-onset short stature, while 27 (2.4%) developed tall stature (>97.5th percentile). Children with systemic arthritis (n = 77) had an estimated 3-year cumulative incidence of 9.3% (95%CI: 4.3-19.7) for new-onset short stature and 34.4% (23-49.4) for obesity. Most children (81.7%) received no systemic corticosteroids, but 1 mg/Kg/day prednisone-equivalent maintained for 6 months corresponded to a drop of 0.64 height Z-scores (0.56-0.82) and an increase of 0.74 BMI Z-scores (0.56-0.92). An increase of 1 in the 10-cm physician global assessment of disease activity maintained for 6 months corresponded to a drop of 0.01 height Z-scores (0-0.02). Most children in this modern JIA cohort grew and gained weight as children in the general population. About 1 in 10 children who had systemic arthritis, uncontrolled disease and/or prolonged corticosteroid use, had increased risk of growth impairment.

Substance use and sexual function in juvenile idiopathic arthritis.

PubMed

van Weelden, Marlon; Lourenço, Benito; Viola, Gabriela R; Aikawa, Nadia E; Queiroz, Lígia B; Silva, Clovis A

2016-02-13

to evaluate alcohol/tobacco/illicit drug use and sexual function in adolescent juvenile idiopathic arthritis (JIA) and healthy controls. 174 adolescents with pediatric rheumatic diseases were selected. A cross-sectional study with 54 JIA patients and 35 controls included demographic/anthropometric data and puberty markers assessments, physician-conducted CRAFFT (car/relax/alone/forget/friends/trouble) screen tool for substance abuse/dependence high risk and a questionnaire that evaluated sexual function, bullying and alcohol/tobacco/illicit drug use. Clinical/laboratorial data and treatment were also assessed in JIA. The median current age was similar between JIA patients and controls [15(10-19) vs. 15(12-18)years, p=0.506]. Frequencies of alcohol/tobacco/illicit drug use were high and similar in both JIA and controls (43% vs. 46%, p=0.829). However, age at alcohol onset was significantly higher in those with JIA [15(11-18) vs. 14(7-18)years, p=0.032], particularly in poliarticular onset (p=0.040). High risk for substance abuse/dependence (CRAFFT score≥2) was found in both groups (13% vs. 15%, p=1.000), likewise bullying (p=0.088). Further analysis of JIA patients regarding alcohol/tobacco/illicit drug use showed that the median current age [17(14-19) vs. 13(10-19)years, p<0.001] and education years [11(6-13) vs. 7(3-12)years, p<0.001] were significant higher in those that used substances. Sexual activity was significantly higher in the former group (48% vs. 7%, p<0.001). A positive correlation was evidenced between CRAFFT score and current age in JIA patients (p=0.032, r=+0.296). A high risk for substance abuse/dependence was observed in both JIA and controls. JIA substance users were more likely to have sexual intercourse. Therefore, routine screening is suggested in all visits of JIA adolescents. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

Substance use and sexual function in juvenile idiopathic arthritis.

PubMed

van Weelden, Marlon; Lourenço, Benito; Viola, Gabriela R; Aikawa, Nadia E; Queiroz, Lígia B; Silva, Clovis A

2016-01-01

To evaluate alcohol/tobacco/illicit drug use and sexual function in adolescent juvenile idiopathic arthritis (JIA) and healthy controls. 174 adolescents with pediatric rheumatic diseases were selected. A cross-sectional study with 54 JIA patients and 35 controls included demographic/anthropometric data and puberty markers assessments, physician-conducted CRAFFT (car/relax/alone/forget/friends/trouble) screen tool for substance abuse/dependence high risk and a questionnaire that evaluated sexual function, bullying and alcohol/tobacco/illicit drug use. Clinical/laboratorial data and treatment were also assessed in JIA. The median current age was similar between JIA patients and controls [15(10-19) vs. 15(12-18) years, p=0.506]. Frequencies of alcohol/tobacco/illicit drug use were high and similar in both JIA and controls (43% vs. 46%, p=0.829). However, age at alcohol onset was significantly higher in those with JIA [15(11-18) vs. 14(7-18) years, p=0.032], particularly in polyarticular onset (p=0.040). High risk for substance abuse/dependence (CRAFFT score≥2) was found in both groups (13% vs. 15%, p=1.000), likewise bullying (p=0.088). Further analysis of JIA patients regarding alcohol/tobacco/illicit drug use showed that the median current age [17(14-19) vs. 13(10-19)years, p<0.001] and education years [11(6-13) vs. 7(3-12)years, p<0.001] were significant higher in those that used substances. Sexual activity was significantly higher in the former group (48% vs. 7%, p<0.001). A positive correlation was evidenced between CRAFFT score and current age in JIA patients (p=0.032, r=+0.296). A high risk for substance abuse/dependence was observed in both JIA and controls. JIA substance users were more likely to have sexual intercourse. Therefore, routine screening is suggested in all visits of JIA adolescents. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

Growth Outcomes After GH Therapy of Patients Given Long-Term Corticosteroids for Juvenile Idiopathic Arthritis.

PubMed

David, Hélène; Aupiais, Camille; Louveau, Baptiste; Quartier, Pierre; Jacqz-Aigrain, Evelyne; Carel, Jean-Claude; Simon, Dominique

2017-12-01

Growth hormone (GH) therapy may improve statural growth outcomes in patients with severe juvenile idiopathic arthritis (JIA). To evaluate the effect of GH treatment on adult height and to identify determinants of growth outcomes in JIA. Data from 58 patients with JIA, including 53 receiving GH, enrolled in three prospective clinical trials between 1997 and 2002 were analyzed. GH (0.056 mg/kg/d [interquartile range (IQR), 0.050 to 0.062]) for a median duration of 6.5 years (IQR, 4.7 to 7.9 years). Factors associated with a favorable growth outcome (adult height - target height ≤ -1.5 standard deviations) were identified by multivariate logistic regression. Adult height was available for 48 patients 8.6 years after GH initiation (IQR, 6.0 to 10.2 years). Height standard deviation score (SDS) increased from -2.9 (IQR, -4.4 to -1.6) at baseline to -1.7 (IQR, -3.9 to -0.1) in adulthood (P < 0.001). Median adult height was below target height [SDS, -0.2 (IQR, -1.4 to 0.4); P < 0.001]. Corrected adult height SDS was -1.3 (IQR, -3.0 to -0.2). Growth outcome was favorable in 24 (52.2%) patients. Significant independent determinants of growth outcome were age at GH initiation [adjusted odds ratio (aOR), 0.68 per additional year; 95% confidence interval (CI), 0.47 to 0.99], height at GH initiation (aOR, 2.6 per additional SDS; 95% CI, 1.15 to 5.9), and mean C-reactive protein levels during follow up (aOR, 0.51 per additional 10 mg/L; 95% CI, 0.28 to 0.92). Long-term GH treatment significantly increased growth in patients with JIA but did not fully restore the genetic growth potential. The response showed marked interindividual variability and was weaker in patients with severe inflammation. Copyright © 2017 Endocrine Society

CONTRAIS: CONservative TReatment for Adolescent Idiopathic Scoliosis: a randomised controlled trial protocol.

PubMed

Abbott, Allan; Möller, Hans; Gerdhem, Paul

2013-09-05

Idiopathic scoliosis is a three-dimensional structural deformity of the spine that occurs in children and adolescents. Recent reviews on bracing and exercise treatment have provided some evidence for effect of these interventions. The purpose of this study is to improve the evidence base regarding the effectiveness of conservative treatments for preventing curve progression in idiopathic scoliosis. Previously untreated girls and boys with idiopathic scoliosis, 9 to 17 years of age with at least one year of remaining growth and a curve Cobb angle of 25-40 degrees will be included. A total of 135 participants will be randomly allocated in groups of 45 patients each to receive one of the three interventions. All three groups will receive a physical activity prescription according to the World Health Organisation recommendations. One group will additionally wear a hyper-corrective night-time brace. One group will additionally perform postural scoliosis-specific exercises. Participation in the study will last until the curve has progressed, or until cessation of skeletal growth. OUTCOME variables will be measured every 6 months. The primary outcome variable, failure of treatment, is defined as progression of the Cobb angle more than 6 degrees, compared to the primary x-ray, seen on two consecutive spinal standing x-rays taken with 6 months interval. Secondary outcome measures include the SRS-22r and EQ5D-Y quality of life questionnaires, the International Physical Activity Questionnaire (IPAQ) short form, and Cobb angle at end of the study. This trial will evaluate which of the tested conservative treatment approaches that is the most effective for patients with adolescent idiopathic scoliosis. NCT01761305.

Anti-adalimumab antibodies in a cohort of patients with juvenile idiopathic arthritis: incidence and clinical correlations.

PubMed

Marino, Achille; Real-Fernández, Feliciana; Rovero, Paolo; Giani, Teresa; Pagnini, Ilaria; Cimaz, Rolando; Simonini, Gabriele

2018-05-01

Adalimumab is a TNF-α blocker antibody similar in structure and function to natural human IgG1. Even if adalimumab is fully humanized, the development of anti-drug antibodies has been reported in several inflammatory conditions. The objective of our study was to assess the presence of anti-adalimumab antibodies (AAA) and their clinical relevance in a cohort of juvenile idiopathic arthritis (JIA) patients on adalimumab. This is a prospective observational cohort study recruiting JIA children. Experiments were performed using a validated surface plasmon resonance (SPR)-based optical assay (Biacore® T100). Disease activity was evaluated using the Juvenile Arthritis Disease Activity Score with 10 joint count (JADAS-10). The Mann-Whitney U test, Wilcoxon signed-rank test for paired samples, chi-square, and Fisher exact test were used to compare data. Pearson's and Spearman's correlation tests were used to determine correlation coefficients for entered variables: demographic, clinical, and serological data. Ten (37%) out of 27 patients included in the study had at least one AAA-positive sample. Patients developed AAA between 3 and 38 months after starting adalimumab. Seven (70%) out of 10 children with AAA positivity experienced at least a relapse compared to 4 (23.5%) out of 17 AAA-negative children (r s 0.45, p < 0.017). In conclusion, using an innovative and accurate assay method, we found a high incidence of anti-drug antibodies in a cohort of adalimumab-treated JIA patients observed over a mean period of 40 weeks; the presence of anti-adalimumab antibodies seemed to be related to the number of relapses.

Blueberry Improves the Therapeutic Effect of Etanercept on Patients with Juvenile Idiopathic Arthritis: Phase III Study.

PubMed

Zhong, Yingjie; Wang, Ye; Guo, Jun; Chu, Haifeng; Gao, Yong; Pang, Limin

2015-11-01

Juvenile idiopathic arthritis (JIA) is the most common arthritis in the adolescents under the age of 16. Etanercept, an inhibitor of tumor necrosis factor, is often used to treat JIA despite its significant side effects. Homeopathic remedies, such as blueberries, have anti-inflammatory properties with fewer unwanted effects and should be considered as a primary treatment. We aimed to explore the efficacy and safety of combination therapy of blueberry and etanercept for JIA. Two hundred and one JIA patients were selected, and randomly and evenly assigned to three groups: ETA (50 mg of etanercept twice weekly), ETABJ (matched etanercept and 50 ml blueberry juice daily) and ETAPJ (matched etanercept and placebo juice). The severity of JIA was measured using American College of Rheumatology scales (ACR) 20, 50 and 70. The levels of pro-inflammatory cytokines, interleukin-1 (IL1) alpha and IL1 beta, and interleukin-1 receptor antagonist (IL1RA) were measured by qRT-PCR and ELISA. After a 6-month follow-up, the ACR20, ACR50 and ACR70 in an ETABJ group were higher than those in other two groups (P < 0.05), suggesting clinically meaningful improvement in JIA. Meanwhile, the symptoms and side effects were reduced significantly or absent in an ETABJ group, including mental diseases, retrobulbar optic neuritis, gaining weight, infection, cutaneous vasculitis, diarrhea, uveitis and pancytopenia. Blueberries reduced the levels of IL1 alpha and beta, and increased the level of IL1RA. Thus, a combination therapy of blueberry and etanercept can reduce the severity of JIA and should be developed as a new method for JIA therapy.

Fulminant bilateral papilloedema during low-dose steroid taper in a child with systemic idiopathic arthritis treated with tocilizumab.

PubMed

Burstzyn, Lulu; Levin, Simon; Rotenberg, Brian; Van Hooren, Tamara; Leung, Andrew; Berard, Roberta; Ardelean, Daniela S

2017-01-01

Systemic juvenile idiopathic arthritis (SJIA) is one of the most severe forms of arthritis that affects children younger than 16 years of age at onset. SJIA often requires corticosteroids to control the inflammation. However, long-term corticosteroid use may have adverse effects, including intracranial hypertension (IH). Biologic therapies have been used as corticosteroid sparing agents. We report the first case of a child with steroid-dependent SJIA treated with tocilizumab, an IL-6 receptor monoclonal antibody, who developed fulminant IH, bilateral papilloedema and vision loss when oral prednisone was weaned from 2 to 1 mg per day. Despite repeated lumbar punctures and high dose acetazolamide, he required urgent unilateral optic nerve sheath fenestration (ONSF). This endoscopic surgical intervention released the pressure exerted by the cerebrospinal fluid on the optic nerve and stopped the progression of vision loss. Nine weeks after the diagnosis of bilateral papilloedema, his vision was completely restored in one eye and partially recovered in the contralateral one. Long-term treatment with corticosteroids even at very low dose and tocilizumab may predispose to severe IH, papilloedema and vision loss. The role that tocilizumab might have played in this case in unclear. Early recognition and prompt treatment of papilloedema is crucial in avoiding permanent vision loss. Fulminant papilloedema in an immunocompromised child carries additional significant challenges. Early ONSF is a safe and effective intervention in refractory papilloedema. Children with severe papilledema secondary to IH should be managed by a multidisciplinary team in tertiary centres.

Azathioprine as a treatment option for uveitis in patients with juvenile idiopathic arthritis.

PubMed

Goebel, J C; Roesel, M; Heinz, C; Michels, H; Ganser, G; Heiligenhaus, A

2011-02-01

To investigate the therapeutic value of azathioprine as monotherapy or combined with other immunosuppressive drugs for uveitis in patients with juvenile idiopathic arthritis (JIA). A retrospective multicentre study including 41 children with JIA (28 (68.2%) female) with unilateral or bilateral (n=28) chronic anterior uveitis. Azathioprine was used to treat uveitis that was active in patients receiving topical or systemic corticosteroids, methotrexate or other immunosuppressive drugs. The primary end point was assessment of uveitis inactivity. Secondary end points comprised dose sparing of topical steroids and systemic corticosteroids, and immunosuppression. At 1 year, uveitis inactivity was achieved in 13/17 (76.5%) patients by using azathioprine as systemic monotherapy and in 5/9 (56.6%) as combination therapy. During the entire azathioprine treatment period (mean 26 months), inactivity was obtained in 16/26 patients (61.5%) with monotherapy and in 10/15 (66.7%) when combined with other immunosuppressives (p=1.0). With azathioprine, dosages of systemic immunosuppression and steroids could be reduced by ≥ 50% (n=12) or topical steroids reduced to ≤ 2 drops/eye/day in six patients. In three patients (7.3%), azathioprine was discontinued because of nausea and stomach pain. Conclusions Azathioprine may be reconsidered in the stepladder approach for the treatment of JIA-associated uveitis. The addition of azathioprine may also be beneficial for patients not responding properly to methotrexate.

Association of IRF5 polymorphisms with susceptibility to macrophage activation syndrome in patients with juvenile idiopathic arthritis.

PubMed

Yanagimachi, Masakatsu; Naruto, Takuya; Miyamae, Takako; Hara, Takuma; Kikuchi, Masako; Hara, Ryoki; Imagawa, Tomoyuki; Mori, Masaaki; Sato, Hidenori; Goto, Hiroaki; Yokota, Shumpei

2011-04-01

Systemic-onset juvenile idiopathic arthritis (systemic JIA) and macrophage activation syndrome (MAS), the most devastating complication of systemic JIA, are characterized by abnormal levels of proinflammatory cytokines. Interferon regulatory factor 5 (IRF5) is a member of the IRF family of transcription factors, and acts as a master transcription factor in the activation of genes encoding proinflammatory cytokines. Polymorphisms in the IRF5 gene have been associated with susceptibility to autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. Our aim was to assess associations of IRF5 gene polymorphisms with susceptibility to systemic JIA and MAS. Three IRF5 single-nucleotide polymorphisms (rs729302, rs2004640, and rs2280714) were genotyped using TaqMan assays in 81 patients with systemic JIA (33 with MAS, 48 without) and 190 controls. There were no associations of the IRF5 gene polymorphisms or haplotypes under study with susceptibility to systemic JIA. There was a significant association of the rs2004640 T allele with MAS susceptibility (OR 4.11; 95% CI 1.84, 9.16; p = 0.001). The IRF5 haplotype (rs729302 A, rs2004640 T, and rs2280714 T), which was reported as conferring an increased risk of SLE, was significantly associated with MAS susceptibility in patients with systemic JIA (OR 4.61; 95% CI 1.73, 12.3; p < 0.001). IRF5 gene polymorphism is a genetic factor influencing susceptibility to MAS in patients with systemic JIA, and IRF5 contributes to the pathogenesis of MAS in these patients.

Changes in body mass index in children with juvenile idiopathic arthritis treated with tumor necrosis factor inhibitors.

PubMed

Shafferman, Ashley; Fontaine, Kevin R; Cron, Randy Q; Beukelman, Timothy

2014-01-01

To evaluate changes in body mass index (BMI) among cohorts of children with juvenile idiopathic arthritis (JIA) with and without tumor necrosis factor (TNF) inhibitor therapy. We performed a retrospective chart review of children with JIA who newly initiated TNF inhibitor therapy and had at least 1 year of subsequent followup (TNF cohort). We also included children with JIA and at least 1 year of followup without any TNF inhibitor therapy (comparator cohort). Children with systemic arthritis were excluded. Age and sex specific BMI z-scores and their corresponding categories (normal, overweight, obese) were determined. We compared changes from a baseline visit to the last followup visit using t-test for BMI z-scores and chi square and Kruskal-Wallis tests for BMI categories. The TNF cohort had 167 patients; the comparator cohort had 37. The median study followup was 2.8 and 2.2 years, respectively. The cohorts had similar age, sex, race, weight, and height distributions. The TNF cohort had a statistically significant increase in BMI z-score from baseline (+0.15; p = 0.02) that was not significantly different from the increase (+0.09) observed in the comparator cohort (p = 0.5). There was no significant change in the proportions of overweight and obese children in the TNF cohort compared to baseline (p = 0.6) or compared to the change in the comparator cohort (p = 0.2). Over more than 2 years of followup, we did not observe a significant increase in BMI among children with JIA receiving TNF inhibitor compared to those not receiving it.

Juvenile idiopathic arthritis-and now?: a systematic literature review of changes in craniofacial morphology.

PubMed

von Bremen, Julia; Ruf, Sabine

2012-08-01

To conduct a systematic literature review on the impact of juvenile idiopathic arthritis (JIA) on craniofacial morphology. Several electronic databases (PubMed, Medpilot, Web of Science, DIMDI) were systematically searched for studies that were published up to and including May 2011. In addition, a manual search of the orthodontic and rheumatologic literature was conducted, and reference lists of the selected articles were checked for relevant publications. The identified articles were independently assessed by two investigators and selected according to a three-step process (title/abstract/full text). After completion of the selection procedure, 19 articles were identified possessing great heterogeneity. In most of them, no differentiated analysis of the various JIA subtypes was performed, and type-specific analyses according to mandibular joint effects were seldom. Additional factors such as patient age, disease duration, medication, previous orthodontic treatment as well as the inclusion of a control group were also highly inhomogeneous, which made a meta-analysis of the data impossible. Nevertheless, it appears as if JIA patients tend to develop a hyperdivergent vertical jaw base relationship and a skeletal Class II pattern. Due to the heterogeneous patient samples, it is currently not possible to draw a differentiated conclusion on the influence of various types of JIA on craniofacial morphology.

Application of Rasch analysis to the parent adherence report questionnaire in juvenile idiopathic arthritis.

PubMed

Toupin April, Karine; Higgins, Johanne; Ehrmann Feldman, Debbie

2016-07-28

Adherence to treatment in children with juvenile idiopathic arthritis (JIA) is associated with better outcomes. Assessing patient adherence in JIA, as well as attitudes and beliefs about prescribed treatments, is important for the clinician in order to optimize patient management. The objective of the current study was to evaluate the psychometric properties of the Parent (proxy-report) Adherence Report Questionnaires (PARQ), which assesses beliefs and behaviors related to adherence to treatments prescribed for JIA. A Rasch analysis was conducted on data collected with parents of children with JIA from two studies in which the PARQ was used as a measure of adherence. The PARQ showed preliminary evidence of multidimensionality with two factors, accounting for 38 % and 27 % of the variance respectively. The PARQ in its original version does not adhere to expectations of the Rasch model. A transformed version of the PARQ obtained by deletion of the general adherence scale and modification of visual analog scales into 5-point likert scales improved fit to the model and showed preliminary evidence of unidimensionality. The PARQ was transformed based on the results of the Rasch analysis. The transformed version of the PARQ shows preliminary evidence of unidimensionality and may allow computation of a total score, although further testing is needed to verify these findings.

Comparison of intra-articular triamcinolone hexacetonide and triamcinolone acetonide in oligoarticular juvenile idiopathic arthritis.

PubMed

Zulian, F; Martini, G; Gobber, D; Agosto, C; Gigante, C; Zacchello, F

2003-10-01

To compare the efficacy and safety of intra-articular triamcinolone hexacetonide (TH) and triamcinolone acetonide (TA) in children with oligoarticular juvenile idiopathic arthritis (JIA). One hundred and thirty joints of 85 patients undergoing intra-articular injections were randomly treated with either TH or TA depending on the availability of the drug. The efficacy of both treatments was evaluated prospectively in a blinded fashion. A good response was defined as a decrease in the articular score of > or =60% from baseline. Clinical, laboratory and immunological variables were noted in order to examine possible factors, other than treatment, predictive of the result. Seventy injections were performed using TH and 60 with TA. The two groups were comparable for clinical, immunological and laboratory characteristics. The rate of response was significantly higher with TH than with TA: 81.4% vs 53.3% (P = 0.001) at 6 months, 67.1 vs 43.3% (P = 0.006) at 12 months, and 60 vs 33.3% (P = 0.002) at 24 months. At comparable doses TH appeared to be much more effective than TA for intra-articular use, in both short- and long-term follow-up. This result was not affected by disease duration or degree of local and systemic inflammation.

Health related quality of life and parental perceptions of child vulnerability among parents of a child with juvenile idiopathic arthritis: results from a web-based survey

PubMed Central

2014-01-01

Background A chronic illness, such as Juvenile Idiopathic Arthritis (JIA), has an impact on the whole family, especially on parents caring for the ill child. Therefore the aim of this study is to evaluate parental Health Related Quality of Life (HRQOL) and parental perceptions of child vulnerability (PPCV) and associated variables in parents of a child with JIA. Methods Parents of all JIA patients (0–18 years) in Amsterdam, the Netherlands, were eligible. HRQOL was measured using the TNO-AZL Questionnaire (TAAQOL) and PPCV using the Child Vulnerability Scale (CVS). The HRQOL of parents of a child with JIA was compared to a norm population, and differences between parents of a child with JIA and active arthritis versus parents of a child with JIA without active arthritis were analyzed (ANOVA). For PPCV, parents of a child with JIA were compared to a norm population, including healthy and chronically ill children (Chi2, Mann-Whitney U test). Variables associated with PPCV were identified by logistic regression analyses. Results 155 parents (87.5% mothers) completed online questionnaires. JIA parents showed worse HRQOL than parents of healthy children on one out of twelve domains: fine motor HRQOL (p < .001). Parents of children with active arthritis showed worse HRQOL regarding daily activities (p < .05), cognitive functioning (p < .01) and depressive emotions (p < .05) compared to parents of children without active arthritis. Parents of children with JIA perceived their child as more vulnerable than parents of a healthy child (p < .001) and parents of a chronically ill child (p < .001). Parents of children with active arthritis reported higher levels of PPCV (p < .05) than parents of children without active arthritis. A higher degree of functional disability (p < .01) and shorter disease duration (p < .05) were associated with higher levels of PPCV. Conclusion The HRQOL of JIA parents was comparable to the HRQOL of parents of a

Health related quality of life and parental perceptions of child vulnerability among parents of a child with juvenile idiopathic arthritis: results from a web-based survey.

PubMed

Haverman, Lotte; van Oers, Hedy A; Maurice-Stam, Heleen; Kuijpers, Taco W; Grootenhuis, Martha A; van Rossum, Marion Aj

2014-01-01

A chronic illness, such as Juvenile Idiopathic Arthritis (JIA), has an impact on the whole family, especially on parents caring for the ill child. Therefore the aim of this study is to evaluate parental Health Related Quality of Life (HRQOL) and parental perceptions of child vulnerability (PPCV) and associated variables in parents of a child with JIA. Parents of all JIA patients (0-18 years) in Amsterdam, the Netherlands, were eligible. HRQOL was measured using the TNO-AZL Questionnaire (TAAQOL) and PPCV using the Child Vulnerability Scale (CVS). The HRQOL of parents of a child with JIA was compared to a norm population, and differences between parents of a child with JIA and active arthritis versus parents of a child with JIA without active arthritis were analyzed (ANOVA). For PPCV, parents of a child with JIA were compared to a norm population, including healthy and chronically ill children (Chi(2), Mann-Whitney U test). Variables associated with PPCV were identified by logistic regression analyses. 155 parents (87.5% mothers) completed online questionnaires. JIA parents showed worse HRQOL than parents of healthy children on one out of twelve domains: fine motor HRQOL (p < .001). Parents of children with active arthritis showed worse HRQOL regarding daily activities (p < .05), cognitive functioning (p < .01) and depressive emotions (p < .05) compared to parents of children without active arthritis. Parents of children with JIA perceived their child as more vulnerable than parents of a healthy child (p < .001) and parents of a chronically ill child (p < .001). Parents of children with active arthritis reported higher levels of PPCV (p < .05) than parents of children without active arthritis. A higher degree of functional disability (p < .01) and shorter disease duration (p < .05) were associated with higher levels of PPCV. The HRQOL of JIA parents was comparable to the HRQOL of parents of a healthy child. JIA parents of a child

Genome-wide data reveal novel genes for methotrexate response in a large cohort of juvenile idiopathic arthritis cases.

PubMed

Cobb, J; Cule, E; Moncrieffe, H; Hinks, A; Ursu, S; Patrick, F; Kassoumeri, L; Flynn, E; Bulatović, M; Wulffraat, N; van Zelst, B; de Jonge, R; Bohm, M; Dolezalova, P; Hirani, S; Newman, S; Whitworth, P; Southwood, T R; De Iorio, M; Wedderburn, L R; Thomson, W

2014-08-01

Clinical response to methotrexate (MTX) treatment for children with juvenile idiopathic arthritis (JIA) displays considerable heterogeneity. Currently, there are no reliable predictors to identify non-responders: earlier identification could lead to a targeted treatment. We genotyped 759 JIA cases from the UK, the Netherlands and Czech Republic. Clinical variables were measured at baseline and 6 months after start of the treatment. In Phase I analysis, samples were analysed for the association with MTX response using ordinal regression of ACR-pedi categories and linear regression of change in clinical variables, and identified 31 genetic regions (P<0.001). Phase II analysis increased SNP density in the most strongly associated regions, identifying 14 regions (P<1 × 10(-5)): three contain genes of particular biological interest (ZMIZ1, TGIF1 and CFTR). These data suggest a role for novel pathways in MTX response and further investigations within associated regions will help to reach our goal of predicting response to MTX in JIA.

Comics as an educational tool for children with juvenile idiopathic arthritis.

PubMed

Mendelson, Amir; Rabinowicz, Noa; Reis, Yonit; Amarilyo, Gil; Harel, Liora; Hashkes, Philip J; Uziel, Yosef

2017-09-02

This study examined whether the comic book Neta and the Medikidz Explain JIA would improve disease-related knowledge and treatment adherence among patients with juvenile idiopathic arthritis (JIA). In this prospective cohort study, JIA patients answered 20 multiple-choice knowledge questions about their disease, before and after reading the comic book. Demographic, clinical, health-related quality of life and adherence data were recorded and correlated to the responses. We studied 61 patients with a mean age of 14 ± 3.3 (range 8-18) years, 67% female, 83% Jewish and 17% non-Jewish. Thirty-nine percent had oligoarthritis, 13% systemic, 32% polyarthritis 11% psoriatic and 5% enthesitis-related type JIA. The disease was active in 46%, 40% were treated with biologics/disease modifying anti-rheumatic drugs, and 34% were in remission on medication. Among the 53 patients who completed before and after quizzes, average score increased from 63 to 80% (P < 0.001). Non-Jewish patients initially scored lower than Jewish patients (48%), but their score increased to 79% after reading the comic book. Twenty-seven patients who also completed the quiz 1 year after the first reading retained their knowledge (79%). We did not find a statistically significant correlation between knowledge and age, sex, disease subtype, or Child Health Questionnaire quality of life scores. Adherence to medication use, physical therapy and rheumatology clinic visits were high at baseline; thus, these did not change after reading the comic. The comic booklet Neta and the Medikidz Explain JIA is a good educational tool for increasing disease-related knowledge in children with JIA.

Parents' willingness to pay for biologic treatments in juvenile idiopathic arthritis.

PubMed

Burnett, Heather F; Ungar, Wendy J; Regier, Dean A; Feldman, Brian M; Miller, Fiona A

2014-12-01

Biologic therapies are considered the standard of care for children with the most severe forms of juvenile idiopathic arthritis (JIA). Inconsistent and inadequate drug coverage, however, prevents many children from receiving timely and equitable access to the best treatment. The objective of this study was to evaluate parents' willingness to pay (WTP) for biologic and nonbiologic disease-modifying antirheumatic drugs (DMARDs) used to treat JIA. Utility weights from a discrete choice experiment were used to estimate the WTP for treatment characteristics including child-reported pain, participation in daily activities, side effects, days missed from school, drug treatment, and cost. Conditional logit regression was used to estimate utilities for each attribute level, and expected compensating variation was used to estimate the WTP. Bootstrapping was used to generate 95% confidence intervals for all WTP estimates. Parents had the highest marginal WTP for improved participation in daily activities and pain relief followed by the elimination of side effects of treatment. Parents were willing to pay $2080 (95% confidence interval $698-$4065) more for biologic DMARDs than for nonbiologic DMARDs if the biologic DMARD was more effective. Parents' WTP indicates their preference for treatments that reduce pain and improve daily functioning without side effects by estimating the monetary equivalent of utility for drug treatments in JIA. In addition to evidence of safety and efficacy, assessments of parents' preferences provide a broader perspective to decision makers by helping them understand the aspects of drug treatments in JIA that are most valued by families. Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Infection rates in patients from five rheumatoid arthritis (RA) registries: contextualising an RA clinical trial programme

PubMed Central

Yamanaka, Hisashi; Askling, Johan; Berglind, Niklas; Franzen, Stefan; Frisell, Thomas; Garwood, Christopher; Greenberg, Jeffrey D; Ho, Meilien; Holmqvist, Marie; Novelli Horne, Laura; Inoue, Eisuke; Michaud, Kaleb; Pappas, Dimitrios A; Reed, George; Symmons, Deborah; Tanaka, Eiichi; Tran, Trung N; Verstappen, Suzanne M M; Wesby-van Swaay, Eveline; Nyberg, Fredrik

2017-01-01

Objective Patients with rheumatoid arthritis (RA) have an increased risk of serious infections. Comparing infection rates across RA populations is complicated by differences in background infection risk, population composition and study methodology. We measured infection rates from five RA registries globally, with the aim to contextualise infection rates from an RA clinical trials population. Methods We used data from Consortium of Rheumatology Research of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (Sweden), Norfolk Arthritis Register (UK), CORRONA International (multiple countries) and Institute of Rheumatology Rheumatoid Arthritis (Japan) and an RA clinical trial programme (fostamatinib). Within each registry, we analysed a main cohort of all patients with RA from January 2000 to last available data. Infection definitions were harmonised across registries. Sensitivity analyses to address potential confounding explored subcohorts defined by disease activity, treatment change and/or prior comorbidities and restriction by calendar time or follow-up. Rates of infections were estimated and standardised to the trial population for age/sex and, in one sensitivity analysis also, for Health Assessment Questionnaire (HAQ) score. Results Overall, age/sex-standardised rates of hospitalised infection were quite consistent across registries (range 1.14–1.62 per 100 patient-years). Higher and more consistent rates across registries and with the trial programme overall were seen when adding standardisation for HAQ score (registry range 1.86–2.18, trials rate 2.92) or restricting to a treatment initiation subcohort followed for 18 months (registry range 0.99–2.84, trials rate 2.74). Conclusion This prospective, coordinated analysis of RA registries provided incidence rate estimates for infection events to contextualise infection rates from an RA clinical trial programme and demonstrated relative comparability of hospitalised infection

Delineating the role of multiple intraarticular corticosteroid injections in the management of juvenile idiopathic arthritis in the biologic era.

PubMed

Papadopoulou, Charalampia; Kostik, Mikhail; Gonzalez-Fernandez, Maria Isabel; Bohm, Marek; Nieto-Gonzalez, Juan Carlos; Pistorio, Angela; Lanni, Stefano; Consolaro, Alessandro; Martini, Alberto; Ravelli, Angelo

2013-07-01

To investigate the outcome and predicting factors of multiple intraarticular corticosteroid (IAC) injections in children with juvenile idiopathic arthritis (JIA). The clinical charts of patients who received their first IAC injection in ≥3 joints between January 2002 and December 2011 were reviewed. The corticosteroid used was triamcinolone hexacetonide for large joints and methylprednisolone acetate for small or difficult to access joints. In each patient, the followup period after IAC injection was censored in case of synovitis flare or at the last visit with continued remission. Predictors included sex, age at disease onset, JIA category, antinuclear antibody (ANA) status, age and disease duration, disease course, general anesthesia, number and type of injected joints, acute-phase reactants, and concomitant systemic medications. A total of 220 patients who had 1,096 joints injected were included. Following IAC therapy, 66.4% of patients had synovitis flare after a median of 0.5 years, whereas 33.6% of patients had sustained remission after a median of 0.9 years. The cumulative probability of survival without synovitis flare was 50.0%, 31.5%, and 19.5% at 1, 2, and 3 years, respectively. On Cox regression analysis, positive C-reactive protein value, negative ANA, lack of concomitant methotrexate administration, and a polyarticular (versus an oligoarticular) disease course were the strongest predictors for synovitis flare. Multiple IAC injection therapy induced sustained remission of joint synovitis in a substantial proportion of patients. A controlled trial comparing multiple IAC injection therapy and methotrexate versus methotrexate and a tumor necrosis factor antagonist is worthy of consideration. Copyright © 2013 by the American College of Rheumatology.

Job retention vocational rehabilitation for employed people with inflammatory arthritis (WORK-IA): a feasibility randomized controlled trial.

PubMed

Hammond, Alison; O'Brien, Rachel; Woodbridge, Sarah; Bradshaw, Lucy; Prior, Yeliz; Radford, Kate; Culley, June; Whitham, Diane; Ruth Pulikottil-Jacob

2017-07-21

Inflammatory arthritis leads to work disability, absenteeism and presenteeism (i.e. at-work productivity loss) at high cost to individuals, employers and society. A trial of job retention vocational rehabilitation (VR) in the United States identified this helped people keep working. The effectiveness of this VR in countries with different socioeconomic policies and conditions, and its impact on absenteeism, presenteeism and health, are unknown. This feasibility study tested the acceptability of this VR, modified for the United Kingdom, compared to written advice about managing work problems. To help plan a randomized controlled trial, we tested screening, recruitment, intervention delivery, response rates, applicability of the control intervention and identified the relevant primary outcome. A feasibility randomized controlled trial with rheumatoid, psoriatic or inflammatory arthritis patients randomized to receive either job retention VR or written information only (the WORK-IA trial). Following three days VR training, rheumatology occupational therapists provided individualised VR on a one to one basis. VR included work assessment, activity diaries and action planning, and (as applicable) arthritis self-management in the workplace, ergonomics, fatigue and stress management, orthoses, employment rights and support services, assistive technology, work modifications, psychological and disclosure support, workplace visits and employer liaison. Fifty five (10%) people were recruited from 539 screened. Follow-up response rates were acceptable at 80%. VR was delivered with fidelity. VR was more acceptable than written advice only (7.8 versus 6.7). VR took on average 4 h at a cost of £135 per person. Outcome assessment indicated VR was better than written advice in reducing presenteeism (Work Limitations Questionnaire (WLQ) change score mean: VR = -12.4 (SD 13.2); control = -2.5 (SD 15.9), absenteeism, perceived risk of job loss and improving pain and health status

Massage Therapy for Pain and Function in Patients With Arthritis: A Systematic Review of Randomized Controlled Trials.

PubMed

Nelson, Nicole L; Churilla, James R

2017-09-01

Massage therapy is gaining interest as a therapeutic approach to managing osteoarthritis and rheumatoid arthritis symptoms. To date, there have been no systematic reviews investigating the effects of massage therapy on these conditions. Systematic review was used. The primary aim of this review was to critically appraise and synthesize the current evidence regarding the effects of massage therapy as a stand-alone treatment on pain and functional outcomes among those with osteoarthritis or rheumatoid arthritis. Relevant randomized controlled trials were searched using the electronic databases Google Scholar, MEDLINE, and PEDro. The PEDro scale was used to assess risk of bias, and the quality of evidence was assessed with the GRADE approach. This review found seven randomized controlled trials representing 352 participants who satisfied the inclusion criteria. Risk of bias ranged from four to seven. Our results found low- to moderate-quality evidence that massage therapy is superior to nonactive therapies in reducing pain and improving certain functional outcomes. It is unclear whether massage therapy is more effective than other forms of treatment. There is a need for large, methodologically rigorous randomized controlled trials investigating the effectiveness of massage therapy as an intervention for individuals with arthritis.

Long-term safety, efficacy, and quality of life in patients with juvenile idiopathic arthritis treated with intravenous abatacept for up to seven years.

PubMed

Lovell, Daniel J; Ruperto, Nicolino; Mouy, Richard; Paz, Eliana; Rubio-Pérez, Nadina; Silva, Clovis A; Abud-Mendoza, Carlos; Burgos-Vargas, Ruben; Gerloni, Valeria; Melo-Gomes, Jose A; Saad-Magalhaes, Claudia; Chavez-Corrales, J; Huemer, Christian; Kivitz, Alan; Blanco, Francisco J; Foeldvari, Ivan; Hofer, Michael; Huppertz, Hans-Iko; Job Deslandre, Chantal; Minden, Kirsten; Punaro, Marilynn; Block, Alan J; Giannini, Edward H; Martini, Alberto

2015-10-01

The efficacy and safety of abatacept in patients with juvenile idiopathic arthritis (JIA) who experienced an inadequate response to disease-modifying antirheumatic drugs were previously established in a phase III study that included a 4-month open-label lead-in period, a 6-month double-blind withdrawal period, and a long-term extension (LTE) phase. The aim of this study was to present the safety, efficacy, and patient-reported outcomes of abatacept treatment (10 mg/kg every 4 weeks) during the LTE phase, for up to 7 years of followup. Patients enrolled in the phase III trial could enter the open-label LTE phase if they had not achieved a response to treatment at month 4 or if they had received abatacept or placebo during the double-blind period. One hundred fifty-three (80.5%) of 190 patients entered the LTE phase, and 69 patients (36.3%) completed it. The overall incidence rate (events per 100 patient-years) of adverse events decreased during the LTE phase (433.61 events during the short-term phase [combined lead-in and double-blind periods] versus 132.39 events during the LTE phase). Similar results were observed for serious adverse events (6.82 versus 5.60), serious infections (1.13 versus 1.72), malignancies (1.12 versus 0), and autoimmune events (2.26 versus 1.18). American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) responses, Pedi 70 responses, and clinically inactive disease status were maintained throughout the LTE phase in patients who continued to receive therapy. Improvements in the Child Health Questionnaire physical and psychosocial summary scores were maintained over time. Long-term abatacept treatment for up to 7 years was associated with consistent safety, sustained efficacy, and quality-of-life benefits in patients with JIA. © 2015 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

Effectiveness of Dexamethasone Iontophoresis for Temporomandibular Joint Involvement in Juvenile Idiopathic Arthritis

PubMed Central

Mina, Rina; Melson, Paula; Powell, Stephanie; Rao, Marepalli; Hinze, Claas; Passo, Murray; Graham, T. Brent; Brunner, Hermine I.

2011-01-01

Objective Temporomandibular joint (TMJ) involvement is common in Juvenile Idiopathic Arthritis (JIA). Dexamethasone iontophoresis (DIP) uses low-grade electric currents for transdermal dexamethasone delivery into deeper anatomic structures. The purpose of this study was to assess the safety and effectiveness of DIP for the treatment of TMJ involvement in JIA, and to delineate variables that are associated with improvement after DIP. Methods Medical records of all JIA patients who underwent DIP for TMJ involvement at a larger tertiary pediatric rheumatology center from 1997 to 2011 were reviewed. DIP was performed using a standard protocol. The effectiveness of DIP was assessed by comparing the maximal inter-incisor opening (MIOTMJ) and the maximal lateral excursion (MLETMJ) before and after treatment. Results Twenty-eight patients (ages 2– 21 years) who received an average of eight DIP treatment sessions per involved TMJ were included in the analysis. Statistically significant improvement in the median MIOTMJ (p< 0.0001) was observed in 68%. The median MLETMJ (p= 0.03) improved in 69%, and resolution of TMJ pain occurred in 73% of the patients who had TMJ pain at baseline. Side effects of DIP were transient site erythema (86%), skin blister (4%), and metallic taste (4%). Improvement in TMJ range of motion from DIP is associated with lower MIOTMJ, lower MLETMJ, and absence of TMJ crepitus at baseline. Conclusion In this pilot study DIP appeared to be an effective and safe initial treatment of TMJ involvement in JIA, especially among patients with decreased TMJ measurements. Prospective controlled studies are needed. PMID:22034112

Development of a national audit tool for juvenile idiopathic arthritis: a BSPAR project funded by the Health Care Quality Improvement Partnership

PubMed Central

McErlane, Flora; Foster, Helen E; Armitt, Gillian; Bailey, Kathryn; Cobb, Joanna; Davidson, Joyce E; Douglas, Sharon; Fell, Andrew; Friswell, Mark; Pilkington, Clarissa; Strike, Helen; Smith, Nicola; Thomson, Wendy; Cleary, Gavin

2018-01-01

Abstract Objective Timely access to holistic multidisciplinary care is the core principle underpinning management of juvenile idiopathic arthritis (JIA). Data collected in national clinical audit programmes fundamentally aim to improve health outcomes of disease, ensuring clinical care is equitable, safe and patient-centred. The aim of this study was to develop a tool for national audit of JIA in the UK. Methods A staged and consultative methodology was used across a broad group of relevant stakeholders to develop a national audit tool, with reference to pre-existing standards of care for JIA. The tool comprises key service delivery quality measures assessed against two aspects of impact, namely disease-related outcome measures and patient/carer reported outcome and experience measures. Results Eleven service-related quality measures were identified, including those that map to current standards for commissioning of JIA clinical services in the UK. The three-variable Juvenile Arthritis Disease Activity Score and presence/absence of sacro-iliitis in patients with enthesitis-related arthritis were identified as the primary disease-related outcome measures, with presence/absence of uveitis a secondary outcome. Novel patient/carer reported outcomes and patient/carer reported experience measures were developed and face validity confirmed by relevant patient/carer groups. Conclusion A tool for national audit of JIA has been developed with the aim of benchmarking current clinical practice and setting future standards and targets for improvement. Staged implementation of this national audit tool should facilitate investigation of variability in levels of care and drive quality improvement. This will require engagement from patients and carers, clinical teams and commissioners of JIA services. PMID:29069424

Development of a national audit tool for juvenile idiopathic arthritis: a BSPAR project funded by the Health Care Quality Improvement Partnership.

PubMed

McErlane, Flora; Foster, Helen E; Armitt, Gillian; Bailey, Kathryn; Cobb, Joanna; Davidson, Joyce E; Douglas, Sharon; Fell, Andrew; Friswell, Mark; Pilkington, Clarissa; Strike, Helen; Smith, Nicola; Thomson, Wendy; Cleary, Gavin

2018-01-01

Timely access to holistic multidisciplinary care is the core principle underpinning management of juvenile idiopathic arthritis (JIA). Data collected in national clinical audit programmes fundamentally aim to improve health outcomes of disease, ensuring clinical care is equitable, safe and patient-centred. The aim of this study was to develop a tool for national audit of JIA in the UK. A staged and consultative methodology was used across a broad group of relevant stakeholders to develop a national audit tool, with reference to pre-existing standards of care for JIA. The tool comprises key service delivery quality measures assessed against two aspects of impact, namely disease-related outcome measures and patient/carer reported outcome and experience measures. Eleven service-related quality measures were identified, including those that map to current standards for commissioning of JIA clinical services in the UK. The three-variable Juvenile Arthritis Disease Activity Score and presence/absence of sacro-iliitis in patients with enthesitis-related arthritis were identified as the primary disease-related outcome measures, with presence/absence of uveitis a secondary outcome. Novel patient/carer reported outcomes and patient/carer reported experience measures were developed and face validity confirmed by relevant patient/carer groups. A tool for national audit of JIA has been developed with the aim of benchmarking current clinical practice and setting future standards and targets for improvement. Staged implementation of this national audit tool should facilitate investigation of variability in levels of care and drive quality improvement. This will require engagement from patients and carers, clinical teams and commissioners of JIA services. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Impact of Antiinflammatory Treatment on the Onset of Uveitis in Juvenile Idiopathic Arthritis: Longitudinal Analysis From a Nationwide Pediatric Rheumatology Database.

PubMed

Tappeiner, Christoph; Schenck, Sandra; Niewerth, Martina; Heiligenhaus, Arnd; Minden, Kirsten; Klotsche, Jens

2016-01-01

Based on a nationwide database, this study analyzed the influence of methotrexate (MTX), tumor necrosis factor (TNF) inhibitors, and a combination of the 2 medications on uveitis occurrence in juvenile idiopathic arthritis (JIA) patients. Data from the National Paediatric Rheumatological Database in Germany were used in this study. Between 2002 and 2013, data from JIA patients were annually documented at the participating pediatric rheumatologic sites. Patients with a JIA disease duration of <12 months at initial documentation and ≥2 years of followup were included in this study. The impact of antiinflammatory treatment on the occurrence of uveitis was evaluated by discrete-time survival analysis. A total of 3,512 JIA patients (mean ± SD age 8.3 ± 4.8 years, 65.7% female, 53.2% antinuclear antibody positive, and mean ± SD age at arthritis onset 7.8 ± 4.8 years) fulfilled the inclusion criteria. Mean ± SD total followup time was 3.6 ± 2.4 years. Uveitis developed in a total of 180 patients (5.1%) within 1 year after arthritis onset. Uveitis onset after the first year was observed in another 251 patients (7.1%). Disease-modifying antirheumatic drug (DMARD) treatment in the year before uveitis onset significantly reduced the risk for uveitis as follows: MTX: hazard ratio (HR) 0.63, P = 0.022; TNF inhibitors: HR 0.56, P < 0.001; and a combination of the 2 medications: HR 0.10, P < 0.001. Patients treated with MTX within the first year of JIA had an even a lower uveitis risk (HR 0.29, P < 0.001). The use of DMARDs in JIA patients significantly reduced the risk for uveitis onset. Early MTX use within the first year of disease and the combination of MTX with a TNF inhibitor had the highest protective effect. © 2016 The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

Foot function is well preserved in children and adolescents with juvenile idiopathic arthritis who are optimally managed

PubMed Central

Hendry, Gordon J.; Rafferty, Danny; Barn, Ruth; Gardner-Medwin, Janet; Turner, Debbie E.; Woodburn, James

2013-01-01

Purpose The objective of this study was to compare disease activity, impairments, disability, foot function and gait characteristics between a well described cohort of juvenile idiopathic arthritis (JIA) patients and normal healthy controls using a 7-segment foot model and three-dimensional gait analysis. Methods Fourteen patients with JIA (mean (standard deviation) age of 12.4 years (3.2)) and a history of foot disease and 10 healthy children (mean (standard deviation) age of 12.5 years (3.4)) underwent three-dimensional gait analysis and plantar pressure analysis to measure biomechanical foot function. Localised disease impact and foot-specific disease activity were determined using the juvenile arthritis foot disability index, rear- and forefoot deformity scores, and clinical and musculoskeletal ultrasound examinations respectively. Mean differences between groups with associated 95% confidence intervals were calculated using the t distribution. Results Mild-to-moderate foot impairments and disability but low levels of disease activity were detected in the JIA group. In comparison with healthy subjects, minor trends towards increased midfoot dorsiflexion and reduced lateral forefoot abduction within a 3–5° range were observed in patients with JIA. The magnitude and timing of remaining kinematic, kinetic and plantar pressure distribution variables during the stance phase were similar for both groups. Conclusion In children and adolescents with JIA, foot function as determined by a multi-segment foot model did not differ from that of normal age- and gender-matched subjects despite moderate foot impairments and disability scores. These findings may indicate that tight control of active foot disease may prevent joint destruction and associated structural and functional impairments. PMID:23142184

Medication use in juvenile uveitis patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance Registry.

PubMed

Henderson, Lauren A; Zurakowski, David; Angeles-Han, Sheila T; Lasky, Andrew; Rabinovich, C Egla; Lo, Mindy S

2016-02-16

There is not yet a commonly accepted, standardized approach in the treatment of juvenile idiopathic uveitis when initial steroid therapy is insufficient. We sought to assess current practice patterns within a large cohort of children with juvenile uveitis. This is a cross-sectional cohort study of patients with uveitis enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRAnet) registry. Clinical information including, demographic information, presenting features, disease complications, and medications were collected. Chi-square and Fisher's exact tests were used to assess for associations between medications and clinical characteristics. Ninety-two children with idiopathic and 656 with juvenile idiopathic arthritis (JIA)-associated uveitis were identified. Indication (arthritis or uveitis) for medication use was not available for JIA patients; therefore, detailed analysis was limited to children with idiopathic uveitis. In this group, 94 % had received systemic steroids. Methotrexate (MTX) was used in 76 % of patients, with oral and subcutaneous forms given at similar rates. In multivariable analysis, non-Caucasians were more likely to be treated initially with subcutaneous MTX (P = 0.003). Of the 53 % of patients treated with a biologic DMARD, all received a tumor necrosis factor (TNF) inhibitor. TNF inhibitor use was associated with a higher frequency of cataracts (52 % vs 21 %; P = 0.001) and antinuclear antibody positivity (49 % vs 29 %; P = 0.04), although overall complication rates were not higher in these patients. Among idiopathic uveitis patients enrolled in the CARRAnet registry, MTX was the most commonly used DMARD, with subcutaneous and oral forms equally favored. Patients who received a TNF inhibitor were more likely to be ANA positive and have cataracts.

Accelerometry-based monitoring of daily physical activity in children with juvenile idiopathic arthritis.

PubMed

Nørgaard, M; Twilt, M; Andersen, L B; Herlin, T

2016-01-01

Juvenile idiopathic arthritis (JIA) may cause functional impairment, reduced participation in physical activity (PA) and, over time, physical deconditioning. The aim of this study was to objectively monitor daily free-living PA in 10-16-year-old children with JIA using accelerometry with regard to disease activity and physical variables and to compare the data with those from healthy age- and gender-matched controls. Patients underwent an evaluation of disease activity, functional ability, physical capacity, and pain. Accelerometer monitoring was assessed using the GT1M ActiGraph. Normative data from two major studies on PA in Danish schoolchildren were used for comparison. Data of accelerometry were available for 61 JIA patients and 2055 healthy controls. Of the JIA patients, 57% showed below-average values of maximal physical capacity (fitness level). JIA patients showed low disease activity and pain and were physically well functioning. Accelerometer counts were lower in JIA patients than in controls. Accelerometer measurements were negatively correlated with disease activity, erythrocyte sedimentation rate (ESR), and number of joints with swelling and/or limited range of motion (ROM). No correlation was found between PA and pain scores, functional ability, and hypermobility. Patients with involvement of ankles or hips demonstrated significantly lower levels of PA. Children with JIA are less physically active and have lower physical capacity and fitness than their age- and gender-matched healthy peers despite good disease control. The involvement of hips or ankles is associated with lower PA.

Ultrasound in management of rheumatoid arthritis: ARCTIC randomised controlled strategy trial

PubMed Central

Aga, Anna-Birgitte; Olsen, Inge Christoffer; Lillegraven, Siri; Hammer, Hilde B; Uhlig, Till; Fremstad, Hallvard; Madland, Tor Magne; Lexberg, Åse Stavland; Haukeland, Hilde; Rødevand, Erik; Høili, Christian; Stray, Hilde; Noraas, Anne; Hansen, Inger Johanne Widding; Bakland, Gunnstein; Nordberg, Lena Bugge; van der Heijde, Désirée; Kvien, Tore K

2016-01-01

Objective To determine whether a treatment strategy based on structured ultrasound assessment would lead to improved outcomes in rheumatoid arthritis, compared with a conventional strategy. Design Multicentre, open label, two arm, parallel group, randomised controlled strategy trial. Setting Ten rheumatology departments and one specialist centre in Norway, from September 2010 to September 2015. Participants 238 patients were recruited between September 2010 and April 2013, of which 230 (141 (61%) female) received the allocated intervention and were analysed for the primary outcome. The main inclusion criteria were age 18-75 years, fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis, disease modifying anti-rheumatic drug naivety with indication for disease modifying drug therapy, and time from first patient reported swollen joint less than two years. Patients with abnormal kidney or liver function or major comorbidities were excluded. Interventions 122 patients were randomised to an ultrasound tight control strategy targeting clinical and imaging remission, and 116 patients were randomised to a conventional tight control strategy targeting clinical remission. Patients in both arms were treated according to the same disease modifying anti-rheumatic drug escalation strategy, with 13 visits over two years. Main outcome measures The primary endpoint was the proportion of patients with a combination between 16 and 24 months of clinical remission, no swollen joints, and non-progression of radiographic joint damage. Secondary outcomes included measures of disease activity, radiographic progression, functioning, quality of life, and adverse events. All participants who attended at least one follow-up visit were included in the full analysis set. Results 26 (22%) of the 118 analysed patients in the ultrasound tight control arm and 21 (19%) of the 112 analysed patients in the

Impact of Juvenile Idiopathic Arthritis Associated Uveitis in Early Adulthood

PubMed Central

Vernie, Lenneke A.; Rothova, Aniki; v. d. Doe, Patricia; Los, Leonoor I.; Schalij-Delfos, Nicoline E.; de Boer, Joke H.

2016-01-01

Background Typically juvenile idiopathic arthritis (JIA)-associated uveitis (further referred as ‘JIA-uveitis’) has its onset in childhood, but some patients suffer its, sometimes visual threatening, complications or ongoing disease activity in adulthood. The objective of this study was to analyze uveitis activity, complications and visual prognosis in adulthood. Methods In this multicenter study, 67 adult patients (129 affected eyes) with JIA-uveitis were retrospectively studied for best corrected visual acuity, visual fields, uveitis activity, topical/systemic treatments, ocular complications, and ocular surgeries during their 18th, 22nd and 30th year of life. Because treatment strategies changed after the year 1990, outcomes were stratified for onset of uveitis before and after 1990. Results Sixty-two of all 67 included patients (93%) had bilateral uveitis. During their 18th life year, 4/52 patients (8%) had complete remission, 28/52 (54%) had uveitis activity and 37/51 patients (73%) were on systemic immunomodulatory treatment. Bilateral visual impairment or legal blindness occurred in 2/51 patients (4%); unilateral visual impairment or legal blindness occurred in 17/51 patients (33%) aged 18 years. The visual prognosis appeared to be slightly better for patients with uveitis onset after the year 1990 (for uveitis onset before 1990 (n = 7) four patients (58%) and for uveitis onset after 1990 (n = 44) 13 patients (30%) were either visual impaired or blind). At least one ocular surgery was performed in 10/24 patients (42%) between their 18th and 22nd year of life. Conclusions Bilateral visual outcome in early adulthood in patients with JIA-uveitis appears to be fairly good, although one third of the patients developed one visually impaired or blind eye. However, a fair amount of the patients suffered from ongoing uveitis activity and needed ongoing treatment as well as surgical interventions. Awareness of these findings is important for ophthalmologists and

Elevated S100A8/A9 and S100A12 Serum Levels Reflect Intraocular Inflammation in Juvenile Idiopathic Arthritis-Associated Uveitis: Results From a Pilot Study.

PubMed

Walscheid, Karoline; Heiligenhaus, Arnd; Holzinger, Dirk; Roth, Johannes; Heinz, Carsten; Tappeiner, Christoph; Kasper, Maren; Foell, Dirk

2015-12-01

Juvenile idiopathic arthritis-associated uveitis (JIAU) is the most common uveitis entity in childhood. As S100A8/A9 and S100A12 proteins are valuable biomarkers in childhood arthritis, we investigated the occurrence of these proteins in childhood uveitis. Serum samples from patients with JIAU (n = 79) or idiopathic anterior uveitis (IAU, n = 24), as well as from nonuveitic controls (n = 24), were collected. Furthermore, aqueous humor samples (JIAU n = 17, nonuveitic controls n = 16, IAU n = 12) were obtained. Samples were analyzed for S100A8/A9 and S100A12 protein levels by ELISA. Intergroup comparisons were performed, involving patient data, clinical data, and S100 levels. S100A8/A9 and S100A12 serum levels were elevated in IAU and JIAU patients as compared to nonuveitic controls (all P < 0.05). S100 serum levels in JIAU patients were higher in active arthritis (not significant; P = 0.289 for S100A8/A9 and P = 0.196 for S100A12) and active uveitis (P = 0.010 for S100A8/A9 and P = 0.026 for S100A12) than in controls. No significant differences in S100 levels were found in a subgroup analysis for sex, antinuclear antibody (ANA) status, disease duration, or presence of uveitis complications. In JIAU patients, S100 serum levels correlated with age and age at onset of uveitis. A longitudinal analysis in JIAU patients showed a correlation of serum S100A8/A9 and S100A12 levels with uveitis activity (both P = 0.03). S100A8/A9 levels in aqueous humor of patients with JIAU (P = 0.001) and IAU (P = 0.0002) were increased as compared to nonuveitic controls. Increased S100A8/A9 and S100A12 levels are found in the serum and aqueous humor of patients with autoimmune uveitis. Serum levels reflect activity of joint and eye disease.

Nonsurgical Management of Adolescent Idiopathic Scoliosis.

PubMed

Gomez, Jaime A; Hresko, M Timothy; Glotzbecker, Michael P

2016-08-01

Pediatric patient visits for spinal deformity are common. Most of these visits are for nonsurgical management of scoliosis, with approximately 600,000 visits for adolescent idiopathic scoliosis (AIS) annually. Appropriate management of scoliotic curves that do not meet surgical indication parameters is essential. Renewed enthusiasm for nonsurgical management of AIS (eg, bracing, physical therapy) exists in part because of the results of the Bracing in Adolescent Idiopathic Scoliosis Trial, which is the only randomized controlled trial available on the use of bracing for AIS. Bracing is appropriate for idiopathic curves between 20° and 40°, with successful control of these curves reported in >70% of patients. Patient adherence to the prescribed duration of wear is essential to maximize the effectiveness of the brace. The choice of brace type must be individualized according to the deformity and the patient's personality as well as the practice setting and brace availability.

Intra-articular corticosteroid injections to the temporomandibular joints are safe and appear to be effective therapy in children with juvenile idiopathic arthritis.

PubMed

Stoll, Matthew L; Good, Jennifer; Sharpe, Tyler; Beukelman, Timothy; Young, Daniel; Waite, Peter D; Cron, Randy Q

2012-08-01

The purpose of this study was to evaluate the safety and efficacy of intra-articular corticosteroid injections (IACIs) of the temporomandibular joint (TMJ) in children with juvenile idiopathic arthritis (JIA) when administered by an oral and maxillofacial surgeon without imaging guidance. This was a retrospective study of children with JIA, seen at a single center, who were selected based on having received IACIs of the TMJ. All subjects received the intervention, which consisted of referral to a single oral and maxillofacial surgeon for TMJ IACI with 5 to 10 mg triamcinolone hexacetonide, under general anesthesia. Primary outcomes assessed in all subjects were the safety of the procedure and efficacy as determined by the change in maximal incisal opening (MIO). In addition, a subset of 31 subjects underwent repeat magnetic resonance imaging of the TMJ, permitting analysis of the change in the acute and chronic findings of arthritis in those patients. Sixty-three patients (68% female) received 137 IACIs. The mean age for diagnosis of JIA was 8.5 years, and the mean age at presentation for TMJ injections was 10 years. The injections were well tolerated: only 1 patient developed the steroid complication of hypopigmentation, and none developed degeneration or ankylosis. In terms of efficacy, the mean MIO increased from 40.8 ± 0.93 to 43.5 ± 0.90 mm (P = .001); in addition, changing the unit of analysis to individual joints, in patients who underwent repeat magnetic resonance imaging examination, 51% of TMJs showed magnetic resonance imaging evidence of improvement of arthritic changes, of whom 18% had complete resolution of TMJ arthritis. The results indicate that IACI of the TMJ can be safely performed by experienced oral and maxillofacial surgeons without a requirement for computed tomographic guidance. In addition, these results show that IACI may be effective in the management of TMJ arthritis, although further studies are required. Copyright © 2012 American

[Recommendations for the use of methotrexate in patients with juvenile idiopathic arthritis].

PubMed

Calvo, I; Antón, J; López Robledillo, J C; de Inocencio, J; Gamir, M L; Merino, R; Lacruz, L; Camacho, M; Rua, M J; Bustabad, S; Díaz Cordovés-Rego, G

2016-03-01

To develop a consensus document of recommendations for the use of methotrexate (MTX) in patients with juvenile idiopathic arthritis (JIA). A group of eleven experts proposed several clinical questions on the use of MTX in patients with JIA. A systematic review was conducted and the evidence and recommendations for each question were extracted. The results were discussed and validated by the experts in a work session to establish the final recommendations. MTX is recommended as the first drug for inducing remission in JIA, and its indication should be made according to the clinical category of the patient. Prior to treatment, it is recommended to perform a complete blood count, including white cells, levels of liver enzymes, serum creatinine, and other analytical parameters according to specific risk factors. Treatment should be initiated with a dose of 10-15 mg/m(2)/week. In cases of uveitis or polyarthritis, an initial dose of 15 mg/m(2)/week should be considered. For a better bioavailability and tolerability, it is preferable to administer MTX parenterally if the dose is ≥15 mg/m(2)/week. It is necessary to periodically perform an analytical monitoring of the patient and to assess possible alterations in liver enzymes to make changes if necessary. Combinations with biological agents may be necessary, as well as the concomitant addition of folic or folinic acid. This document describes the main recommendations for the appropriate use of MTX in JIA patients, according to scientific evidence and clinical experience. Copyright © 2015 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

HLA-B27 predicts a more chronic disease course in an 8-year followup cohort of patients with juvenile idiopathic arthritis.

PubMed

Berntson, Lillemor; Nordal, Ellen; Aalto, Kristiina; Peltoniemi, Suvi; Herlin, Troels; Zak, Marek; Nielsen, Susan; Rygg, Marite

2013-05-01

We investigated associations of HLA-B27 with clinical manifestations and longterm outcome in a near population-based setting among patients with juvenile idiopathic arthritis (JIA). We studied clinical and serological data from 410 patients with HLA-B27 results among 440 prospectively collected patients with JIA with 8-year followup data in a Nordic database. The study was structured to be as close to a population-based study as possible. HLA-B27 was analyzed in 93% of patients, and was positive in 21% of the cohort, in 18.4% of the girls and in 25.9% of the boys. Boys who were HLA-B27-positive had significantly higher age at onset compared to HLA-B27-negative boys and compared to both HLA-B27-negative and positive girls. This difference in onset age in relation to HLA-B27 was not found in girls. HLA-B27 was associated with clinical signs of sacroiliitis, enthesitis, and tenosynovitis in boys, but not in girls. After 8 years of disease, 46 children (11.2%) were classified as having enthesitis-related arthritis (ERA). Boys with ERA had clinical signs of sacroiliitis more often than girls with ERA. HLA-B27-positive children, as well as children with clinical signs of sacroiliitis, enthesitis, and hip arthritis, had higher odds of not being in remission off medication after 8 years of disease. In this near population-based Nordic JIA cohort we found significant differences between HLA-B27-positive boys and girls in age at disease onset, clinical signs of sacroiliitis, and ERA classification. HLA-B27 was negatively associated with longterm remission status, possibly because of its association with clinical disease characteristics, such as sacroiliitis, rather than being a general marker of persistent disease.

Long-term safety of etanercept and adalimumab compared to methotrexate in patients with juvenile idiopathic arthritis (JIA).

PubMed

Klotsche, Jens; Niewerth, Martina; Haas, Johannes-Peter; Huppertz, Hans-Iko; Zink, Angela; Horneff, Gerd; Minden, Kirsten

2016-05-01

Published evidence on the long-term safety of etanercept (ETA) and adalimumab (ADA) in patients with polyarticular juvenile idiopathic arthritis (pJIA) is still limited. To investigate the rates of serious adverse events (SAE) and of events of special interest (ESI) under ETA and ADA treatment. Patients with pJIA were prospectively observed in the national JIA biological register, Biologika in der Kinderrheumatologie, and its follow-up register, Juvenile arthritis Methotrexate/Biologics long-term Observation. We calculated the relative risks of SAE and ESI for ETA and ADA compared with methotrexate (MTX). Among the 1414 patients treated with ETA (n=1414; 4461 exposure years (EY)) and ADA (n=320; 493 EY), significantly more SAE, infections and medically important infections were observed (ETA: 4.5, 5.7, 0.9; ADA: 4.7, 11.4, 0.4 per 100 EY) compared with those treated with MTX alone (n=1455; 2.907 EY; 2.6, 5.5, 0.5 per 100 EY). The risk for malignancies was not significantly increased for ETA and ADA compared with MTX (0.09, 0.27 and 0.07/100 person-years). Patients under ETA monotherapy developed more frequently incident inflammatory bowel disease (IBD) and incident uveitis (0.5 and 0.8/100 EY) than patients treated by ETA in combination with MTX (0.1 and 0.2/100 EY) or MTX alone (0.03 and 0.1/100 EY). Our data confirm the acceptable long-term tolerability of ETA and ADA in pJIA. However, whether the onset of IBD and uveitis during ETA monotherapy is a paradoxical effect or an inadequate response to therapy remains unclear and requires further investigation in this growing cohort. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Health-related quality of life among Swedish children with Juvenile Idiopathic Arthritis: parent-child discrepancies, gender differences and comparison with a European cohort.

PubMed

Lundberg, Veronica; Eriksson, Catharina

2017-04-12

This study investigates gender differences in self-reports and between parent and child reports in Health-related Quality of Life (HRQOL), measured with disease-specific and generic instruments for chronic disease. Comparison of HRQOL results in this Juvenile Idiopathic Arthritis (JIA) sample to a European cohort of children with JIA and one of children with other health conditions are also made. Fifty-three children with juvenile idiopathic arthritis (JIA), aged 8-18 years, and their parents completed the condition-specific DISABKIDS for JIA, and the DISABKIDS generic instrument for chronic conditions (DCGM-37) in a cross-sectional study. European reference data were used for comparison of child and parental reports. Child self-reports in DCGM-37 and DISABKIDS for JIA showed no gender differences. Parental and child reports of the child's HRQOL differed only in DCGM-37; this was among girls who scored their independence (p = 0.03), physical limitation (p = 0.01), social exclusion (p = 0.03), emotions (p <0.01), and general transformed score (p <0.01) higher than did their parents. Our sample of children with JIA reported more physical limitation compared to samples of European children with JIA (p = 0.01), European children with chronic conditions (p < 0.01), and their parents (p = 0.01 and p < 0.01). The Swedish children reported more problem with understanding compared to the European JIA sample (p = 0.03). Swedish parents perceived their children's independence significantly lower than did the European parents of JIA children (p < 0.01), as well as European parents of children with chronic conditions (p = 0.03). The Swedish parents also perceived their children to have significantly lower social inclusion (p < 0.05) and general transformed score (p = 0.04), in comparison to European parents of children with chronic conditions. Parent-child differences in assessment of quality of life depend on the HRQOL instrument

Determinants of health-related quality of life impairment in Egyptian children and adolescents with juvenile idiopathic arthritis: Sharkia Governorate.

PubMed

Abdul-Sattar, Amal B; Elewa, Enass A; El-Shahawy, Eman El-Dessoky; Waly, Eman H

2014-08-01

The aim of this study was to identify the possible determinants of impaired health-related quality of life (HRQOL) in Egyptian children and adolescents with juvenile idiopathic arthritis (JIA). Fifty-eight consecutive patients of JIA aged from 8 to 18 years underwent assessment of socio-economic and demographic characteristics; HRQOL using Pediatric Quality of Life Inventory 4.0 Generic Core Scale, disease activity using the Juvenile Arthritis Disease Activity Score based on 27 joints (JADAS-27), functional ability using the childhood health assessment questionnaire (CHAQ), pain score on visual analog scale and psychological symptoms using the Children's Depression Inventory (CDI) score. Multivariate modeling was applied to determine the factors that associated with HRQOL impairment. A total of 55 % of the patients (32 of 58) had impaired HRQOL (<78.6). In multiple regression analyses, high CHAQ scores (OR 6.0, 95 % CI 2.0-17.5, P = 0.001), pain (OR 3.1, 95 % CI 1.9-6.3, P = 0.01), stop going to school (OR 3.9, 95 % CI 2.0-7.3, P = 0.01), low socioeconomic status (OR 2.3, 95 % CI 1.09-4.7, P = 0.04) and high psychological symptoms (OR 4.2, 95 % CI 2.0-12.6, P = 0.001) were determinants for HRQOL impairment. HRQOL impairment is a significant problem in Egyptian children and adolescents with JIA. These findings underscore the critical need for monitoring of HRQOL in these patients. More attention should be given to JIA patients who stop going to school and who has low socioeconomic status.

Assessment of left atrial mechanical functions and atrial electromechanical delay in Juvenile idiopathic arthritis by tissue Doppler echocardiography.

PubMed

El Eraky, Azza Z; Handoka, Nesrin M; Ghaly, Mona Sayed; Nasef, Samah Ismail; Eldahshan, Nahed A; Ibrahim, Ahmed M; Shalaby, Sherein

2016-11-24

Juvenile idiopathic arthritis (JIA) is a systemic chronic inflammatory disease. Studies using tissue Doppler imaging (TDI) for the evaluation of cardiac functions of children with JIA are limited. Thus, this study was conducted to evaluate Left ventricular function, left atrial mechanical functions and atrial electromechanical delay in JIA. This study was carried out as a across sectional study. A total of 34 patients with active JIA and 34 controls were included. Atrial electromechanical delay and left atrial (LA) mechanical functions in addition to systolic and diastolic left ventricular (LV) functions were measured by using conventional echocardiography and TDI. Assessment of disease activity was done using Juvenile arthritis disease activity score (JADAS-27). JIA patients had abnormal atrial electromechanical coupling as established from prolonged lateral mitral annulus (PA lateral), septal mitral annulus (PA septum), inter-atrial and intra-atrial electromechanical delays compared with healthy controls. Left ventricular filling abnormalities were found characterized by a reduced E/A ratio (1.07 ± 0.56 vs. 1.48 ± 0.16, p = 0.01). E/Em was significantly higher in patients with JIA (7.58 ± 1.79 vs. 4.74 ± 1.45, p = 0.003) denoting impaired diastolic function. Left atrial mechanical functions assessment showed significantly decreased LA passive emptying fraction, increased LA active emptying fraction and LA total emptying volume in JIA patients (p = 0.01, p = 0.01, p = 0.03 respectively). Atrial electromechanical coupling intervals, and LA mechanical functions were impaired which can be considered as an early form of subclinical cardiac involvement in JIA patients. Significant diastolic functional abnormalities exist in JIA.

How do parents of children with juvenile idiopathic arthritis (JIA) perceive their therapies?

PubMed

Rouster-Stevens, Kelly; Nageswaran, Savithri; Arcury, Thomas A; Kemper, Kathi J

2008-06-02

Complementary and alternative medical (CAM) therapies are commonly used by pediatric patients with chronic medical conditions. Little is known about parents' perceptions of these therapies. This study describes the views of parents of patients with juvenile idiopathic arthritis (JIA) regarding conventional and CAM therapies. Parents of children with JIA seen at a pediatric rheumatology clinic were surveyed between June 1 and July 31, 2007. Questionnaires asked about patients' use of over 75 therapies in the past 30 days, their perceived helpfulness (0 = not helpful; 3 = very helpful), perceived side effects (0 = none; 3 = severe), and whether each therapy would be recommended to other patients with JIA (Yes, No, Not sure). Questionnaires were returned by 52/76 (68%) parents; patients' average age was 10.9 years and 87% were Caucasian. Medications were used by 45 (88%) patients; heat (67%) and extra rest (54%) were also commonly used. CAM therapies were used by 48 (92%), e.g., massage (54%), vitamins and other supplements (54%), avoiding foods that worsened pain (35%) and stress management techniques (33%). Among the therapies rated by 3 or more parents, those that scored 2.5 or higher on helpfulness were: biologic medications, methotrexate, naproxen, wheelchairs, orthotics, heat, vitamins C and D, music, support groups and prayer. CAM therapies had 0 median side effects and parents would recommend many of them to other families. JIA patients use diverse therapies. Parents report that many CAM therapies are helpful and would recommend them to other parents. These data can be used in counseling patients and guiding future research.

Associates of school impairment in Egyptian patients with juvenile idiopathic arthritis: Sharkia Governorate.

PubMed

Abdul-Sattar, Amal; Magd, Sahar Abou El; Negm, Mohamed G

2014-01-01

The aim of this study was to investigate the factors associated with school absenteeism and poor school functioning in Egyptian children and adolescents with juvenile idiopathic arthritis (JIA). We studied 52 consecutive patients of JIA with age ≥ 7 years and duration of disease ≥ 1 year. All of the patients underwent assessment of socioeconomic and demographic characteristics, disease activity (JIDAS-27), functional ability (CHAQ), depressive symptoms (CDI score), and school functioning (PedsQL™ 4.0). Multivariate modeling was applied to determine the factors that associated with school absenteeism and poor school functioning. A total of 69% of the sample missed 3 weeks or more of school during past academic year. The mean percentage of missed school days was 12.5% (equivalent to 25 absent days). A total of 46% of the patients had poor school functioning (school functioning subscale score of HRQOL ≥ 1 SD below the mean of healthy children). In multiple regression analyses, high CHAQ scores, disease activity, and depressive symptoms were independent predictors for both of school absenteeism and of poor school functioning. However, living in rural regions was independently associated only with high school absenteeism in patients with JIA. Disease activity, functional disability, and high depressive symptoms are predictors of school absenteeism and poor school functioning. These findings underscore the critical need for treatment strategies that have the ability to better control disease activity, to minimize functional disability, and depressive symptoms. More attention should be given to JIA patients who live in rural regions.

Randomized controlled trial of foot reflexology for patients with symptomatic idiopathic detrusor overactivity.

PubMed

Mak, Ho-Leung Jimmy; Cheon, Willy Cecilia; Wong, To; Liu, Yu Sun John; Tong, Wai Mei Anny

2007-06-01

The aim of this study was to examine whether foot reflexology has beneficial effects on patients with idiopathic detrusor overactivity. One hundred and nine women with symptomatic idiopathic detrusor overactivity were randomized into either foot reflexology treatment group or nonspecific foot massage control group. The primary outcome measure was the change in the diurnal micturition frequency. There was significant change in the number of daytime frequency in the reflexology group when compared with the massage group (-1.90 vs -0.55, p = 0.029). There was also a decrease in the 24-h micturition frequency in both groups, but the change was not statistically significant (-2.80 vs -1.04 p = 0.055). In the reflexology group, more patients believed to have received "true" reflexology (88.9 vs 67.4%, p = 0.012). This reflects the difficulty of blinding in trials of reflexology. Larger scale studies with a better-designed control group and an improved blinding are required to examine if reflexology is effective in improving patients' overall outcome.

Methotrexate for uveitis associated with juvenile idiopathic arthritis: value and requirement for additional anti-inflammatory medication.

PubMed

Heiligenhaus, A; Mingels, A; Heinz, C; Ganser, G

2007-01-01

To study the value of methotrexate (MTX) and the requirement for additional anti-inflammatory drugs for the treatment of severe chronic iridocyclitis associated with juvenile idiopathic arthritis (JIA). Institutional study of 35 consecutive patients with JIA started on MTX as the single systemic immunosuppressive drug for the treatment of associated iridocyclitis. The clinical epidemiologic data, course of visual acuity (VA), development of complications, and the need for additional anti-inflammatory drugs were analyzed. Mean follow-up with MTX treatment was 27.6 months. Uveitic complications were present in 31 patients before MTX treatment. With MTX, quiescence of uveitis was obtained with (n=21) or without (n=4) additional topical steroids. Additional systemic immunosuppressive drugs were required in another 7 patients: cyclosporine A (n=4), azathioprine (n=1), infliximab (n=1), or etanercept (n=1). Three patients had active uveitis at the end of the follow-up period. During MTX therapy, uveitis first developed in the unaffected fellow eyes in 2 patients, and secondary glaucoma or ocular hypertension occurred in 7 patients. The VA deteriorated in 6, improved in 13, and was stable in the remaining eyes. The data suggest that MTX is very effective in controlling inflammation of uveitis in patients with JIA. However, additional topical steroids or systemic immunosuppressive drugs are often required.

Usefulness of Adalimumab in the Treatment of Refractory Uveitis Associated with Juvenile Idiopathic Arthritis

PubMed Central

García-De-Vicuña, Carmen; Díaz-Llopis, Manuel; Salom, David; Bou, Rosa; Díaz-Cascajosa, Jesus; Cordero-Coma, Miguel; Ortega, Gabriela; Ortego-Centeno, Norberto; Suarez-De-Figueroa, Marta; Cruz-Martínez, Juan; Fonollosa, Alex; Blanco, Ricardo; García-Aparicio, Ángel María; Benítez-Del-Castillo, Jose M.; Antón, Jordi

2013-01-01

Purpose. To assess the efficacy and safety of adalimumab in patients with juvenile idiopathic arthritis (JIA) and associated refractory uveitis. Design. Multicenter, prospective case series. Methods. Thirty-nine patients (mean [SD] age of 11.5 [7.9] years) with JIA-associated uveitis who were either not responsive to standard immunosuppressive therapy or intolerant to it were enrolled. Patients aged 13–17 years were treated with 40 mg of adalimumab every other week for 6 months and those aged 4–12 years received 24 mg/m2 body surface. Results. Inflammation of the anterior chamber (2.02 [1.16] versus 0.42 [0.62]) and of the posterior segment (2.38 [2.97] versus 0.35 [0.71] decreased significantly between baseline and the final visit (P < 0.001). The mean (SD) macular thickness at baseline was 304.54 (125.03) μ and at the end of follow-up was 230.87 (31.12) μ (P < 0.014). Baseline immunosuppression load was 8.10 (3.99) as compared with 5.08 (3.76) at the final visit (P < 0.001). The mean dose of corticosteroids also decreased from 0.25 (0.43) to 0 (0.02) mg (P < 0.001). No significant side effects requiring discontinuation of therapy were observed. Conclusion. Adalimumab seems to be an effective and safe treatment for JIA-associated refractory uveitis and may reduce steroid requirement. PMID:24489444

Inflammatory arthritis mimicking Complex Regional Pain Syndrome (CRPS) in a child: A case report.

PubMed

Egilmez, Zeliha; Turgut, Selin Turan; Icagasioglu, Afitap; Bicakci, Irem

2016-01-01

Joint complaints in childhood are seen frequently and differential diagnosis can be difficult. Juvenile idiopathic arthritis (JIA) is the most common rheumatological disease of childhood. It involves peripheral joint arthritis, chronic synovitis, and extra-articular manifestations. Accurate diagnosis can take a long time and sometimes multiple diagnoses are used while following the patient until a final diagnosis can be reached. Arthritis may be triggered by trauma and confused with other diseases like complex regional pain syndrome (CRPS), in which trauma plays a role in the etiology. In the present case, ankle pain in an 8-year-old girl was misdiagnosed as CRPS.

Task-Oriented Training with Computer Games for People with Rheumatoid Arthritis or Hand Osteoarthritis: A Feasibility Randomized Controlled Trial.

PubMed

Srikesavan, Cynthia Swarnalatha; Shay, Barbara; Szturm, Tony

2016-09-13

To examine the feasibility of a clinical trial on a novel, home-based task-oriented training with conventional hand exercises in people with rheumatoid arthritis or hand osteoarthritis. To explore the experiences of participants who completed their respective home exercise programmes. Thirty volunteer participants aged between 30 and 60 years and diagnosed with rheumatoid arthritis or hand osteoarthritis were proposed for a single-center, assessor-blinded, randomized controlled trial ( ClinicalTrials.gov : NCT01635582). Participants received task-oriented training with interactive computer games and objects of daily life or finger mobility and strengthening exercises. Both programmes were home based and were done four sessions per week with 20 minutes each session for 6 weeks. Major feasibility outcomes were number of volunteers screened, randomized, and retained; completion of blinded assessments, exercise training, and home exercise sessions; equipment and data management; and clinical outcomes of hand function. Reaching the recruitment target in 18 months and achieving exercise compliance >80% were set as success criteria. Concurrent with the trial, focus group interviews explored experiences of those participants who completed their respective programmes. After trial initiation, revisions in inclusion criteria were required to promote recruitment. A total of 17 participants were randomized and 15 were retained. Completion of assessments, exercise training, and home exercise sessions; equipment and data collection and management demonstrated excellent feasibility. Both groups improved in hand function outcomes and exercise compliance was above 85%. Participants perceived both programmes as appropriate and acceptable. Participants who completed task-oriented training also agreed that playing different computer games was enjoyable, engaging, and motivating. Findings demonstrate initial evidence on recruitment, feasibility of trial procedures, and acceptability of

[Low bone mineral density in juvenile idiopathic arthritis: Prevalence and related factors].

PubMed

Galindo Zavala, Rocío; Núñez Cuadros, Esmeralda; Martín Pedraz, Laura; Díaz-Cordovés Rego, Gisela; Sierra Salinas, Carlos; Urda Cardona, Antonio

2017-10-01

Height adjustment is currently recommended for Z-score bone mineral density (BMD) assessed by dual energy X-ray absorptiometry. At present there are no studies that evaluate the prevalence of low BMD in paediatric patients with Juvenile Idiopathic Arthritis (JIA) in Spain following current recommendations. To evaluate low BMD in JIA in paediatric patients with JIA in Spain following the latest recommendations, as well as to assess associated factors. Observational cross-sectional study of Spanish JIA patients from 5 to 16 years-old, followed-up in a Paediatric Rheumatology Unit between July 2014 and July 2015. Anthropometric, clinical and treatment data were recorded. Dual energy X-ray absorptiometry, and bone metabolism parameters were collected, and a completed diet and exercise questionnaire was obtained. A total of 92 children participated. The population prevalence estimation of low BMD was less than 5% (95% CI). A significant positive correlation was found in the multiple linear regression analysis between the body mass index percentile (B: 0.021; P<.001) and lean mass index (B: 0.0002; P=.012), and BMD Z-score adjusted for height (Z-SAH). A significant negative correlation was found between fat mass index (B: -0.0001; P=.018) and serum type I collagen N-propeptide (B: -0,0006; P=.036) and Z-SAH. Low BMD prevalence in JIA patients in our population is low. An adequate nutritional status and the prevalence of lean over fat mass seem to promote the acquisition of bone mass. Those JIA patients with lower BMD could be subjected to an increase of bone turnover. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Evidence for Updating the Core Domain Set of Outcome Measures for Juvenile Idiopathic Arthritis: Report from a Special Interest Group at OMERACT 2016.

PubMed

Morgan, Esi M; Riebschleger, Meredith P; Horonjeff, Jennifer; Consolaro, Alessandro; Munro, Jane E; Thornhill, Susan; Beukelman, Timothy; Brunner, Hermine I; Creek, Emily L; Harris, Julia G; Horton, Daniel B; Lovell, Daniel J; Mannion, Melissa L; Olson, Judyann C; Rahimi, Homaira; Gallo, Maria Chiara; Calandra, Serena; Ravelli, Angelo; Ringold, Sarah; Shenoi, Susan; Stinson, Jennifer; Toupin-April, Karine; Strand, Vibeke; Bingham, Clifton O

2017-12-01

The current Juvenile Idiopathic Arthritis (JIA) Core Set was developed in 1997 to identify the outcome measures to be used in JIA clinical trials using statistical and consensus-based techniques, but without patient involvement. The importance of patient/parent input into the research process has increasingly been recognized over the years. An Outcome Measures in Rheumatology (OMERACT) JIA Core Set Working Group was formed to determine whether the outcome domains of the current core set are relevant to those involved or whether the core set domains should be revised. Twenty-four people from the United States, Canada, Australia, and Europe, including patient partners, formed the working group. Guided by the OMERACT Filter 2.0 process, we performed (1) a systematic literature review of outcome domains, (2) a Web-based survey (142 patients, 343 parents), (3) an idea-generation study (120 parents), (4) 4 online discussion boards (24 patients, 20 parents), and (5) a Special Interest Group (SIG) activity at the OMERACT 13 (2016) meeting. A MEDLINE search of outcome domains used in studies of JIA yielded 5956 citations, of which 729 citations underwent full-text review, and identified additional domains to those included in the current JIA Core Set. Qualitative studies on the effect of JIA identified multiple additional domains, including pain and participation. Twenty-one participants in the SIG achieved consensus on the need to revise the entire JIA Core Set. The results of qualitative studies and literature review support the need to expand the JIA Core Set, considering, among other things, additional patient/parent-centered outcomes, clinical data, and imaging data.

A cohort study of patients with juvenile idiopathic arthritis and arthritis of the temporomandibular joint: outcome of arthrocentesis with and without the use of steroids.

PubMed

Olsen-Bergem, H; Bjørnland, T

2014-08-01

The purpose of this study was to evaluate the effects of intra-articular temporomandibular joint (TMJ) treatment in patients with juvenile idiopathic arthritis (JIA). The inclusion criteria were met by 21 patients (38 joints). Joints were randomly selected for either arthrocentesis alone (n=17) or arthrocentesis with the additional use of triamcinolone hexacetonide (n=21) using a closed single-needle system. Measurements of pain and function were performed at baseline and at follow-up after 3 and 8 months. Pain on opening and lateral excursion improved significantly after injections. Pain decreased significantly from baseline to first and second control on a visual analogue scale (VAS) for overall pain (49-18-8) and overall function (41-19-4). Significant improvement was recorded for pain on palpation of muscles and joints. There was no statistically significant difference between the treatment modalities, with or without glucocorticoid injection. Arthrocentesis in the TMJ treatment of patients with JIA may be beneficial and steroids had no additional effect. Further studies are needed to evaluate the long-term effects on the TMJ structures and on condylar growth from arthrocentesis and intra-articular steroid injections. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Generation of novel pharmacogenomic candidates in the response to methotrexate in juvenile idiopathic arthritis: correlation between gene expression and genotype

PubMed Central

Moncrieffe, Halima; Hinks, Anne; Ursu, Simona; Kassoumeri, Laura; Etheridge, Angela; Hubank, Mike; Martin, Paul; Weiler, Tracey; Glass, David N; Thompson, Susan D.; Thomson, Wendy; Wedderburn, Lucy R

2010-01-01

Objectives Little is known about mechanisms of efficacy of methotrexate (MTX) in childhood arthritis, or genetic influences upon response to MTX. The aims of this study were to use gene expression profiling to identify novel pathways/genes altered by MTX and then investigate these genes for genotype associations with response to MTX treatment. Methods Gene expression profiling before and after MTX treatment was performed on 11 children with juvenile idiopathic arthritis (JIA) treated with MTX, in whom response at 6 months of treatment was defined. Genes showing the most differential gene expression after treatment were selected for SNP genotyping. Genotype frequencies were compared between non-responders and responders (ACR-Ped70). An independent cohort was available for validation. Results Gene expression profiling before and after MTX treatment revealed 1222 differentially expressed probes sets (fold change >1.7, p< 0.05) and 1065 when restricted to full responder cases only. Six highly differentially expressed genes were analysed for genetic association to response to MTX. Three SNPs in the SLC16A7 gene showed significant association with MTX response. One SNP showed validated association in an independent cohort. Conclusions This study is the first, to our knowledge, to evaluate gene expression profiles in children with JIA before and after MTX, and to analyse genetic variation in differentially expressed genes. We have identified a gene which may contribute to genetic variability in MTX response in JIA, and established as proof of principle that genes which are differentially expressed at mRNA level after drug administration may also be good candidates for genetic analysis. PMID:20827233

The Use of IL-1 Receptor Antagonist (Anakinra) in Idiopathic Recurrent Pericarditis: A Narrative Review

PubMed Central

Baskar, Shankar; Klein, Allan L.; Zeft, Andrew

2016-01-01

Recurrent pericarditis is a complication of acute pericarditis in 20–30% of the patients and is usually idiopathic in nature. The underlying pathogenesis of this condition remains unclear, although immune-mediated mechanisms seem likely. A subgroup of these patients with refractory symptoms can be challenging to manage, and multiple immunosuppressive medications have been used without consistent benefit. Anakinra, an interleukin-1 receptor antagonist, has been used in treatment of rheumatoid arthritis and autoinflammatory syndromes. Preliminary evidence suggests that anakinra could be a promising therapy for idiopathic recurrent pericarditis. In this narrative review, we summarize the current understanding of the etiopathogenesis of idiopathic recurrent pericarditis, mechanism of action of anakinra, and the preliminary evidence, supporting the use of anakinra in pericarditis. PMID:26942035

Diagnosis of systemic-onset juvenile idiopathic arthritis after treatment for presumed Kawasaki disease.

PubMed

Dong, Siwen; Bout-Tabaku, Sharon; Texter, Karen; Jaggi, Preeti

2015-05-01

To estimate the incidence of systemic-onset juvenile idiopathic arthritis (SoJIA) within 6 months after treatment for presumed Kawasaki disease (KD) (presumed patients with KD with subsequent diagnosis of SoJIA [pKD/SoJIA]) and describe presentation differences from sole KD. We identified patients treated for KD at Nationwide Children's Hospital and from the Pediatric Health Information System from 2009-2013. We then identified the subset of children, pKD/SoJIA, who received an International Classification of Diseases, Ninth Revision code for SoJIA and had it listed at least once 3 months after and within 6 months after KD diagnosis. Demographic characteristics, readmission rates, treatments, and complications were noted. A literature review was also performed to identify clinical, laboratory, and echocardiographic data of previously documented patients with KD later diagnosed with SoJIA. There were 6745 total treated patients with KD in the Pediatric Health Information System database during the study period; 10 patients were identified to have pKD/SoJIA (0.2% of cohort). Those with pKD/SoJIA were predominantly Caucasian compared with patients with KD (90% and 46.8%, respectively; P=.003). Macrophage activation syndrome was more common in patients with pKD/SoJIA than in sole patients with KD (30% and 0.30%, respectively; P<.001). Fifteen cases of pKD/SoJIA were identified by literature and chart review, 12 of whom were initially diagnosed with incomplete KD. We reported a 0.2% incidence of pKD/SoJIA, which was associated with Caucasian race, macrophage activation syndrome, and an incomplete KD phenotype. Copyright © 2015 Elsevier Inc. All rights reserved.

Multiplex Cytokine Analysis of Aqueous Humor in Juvenile Idiopathic Arthritis-Associated Anterior Uveitis With or Without Secondary Glaucoma.

PubMed

Bauer, Dirk; Kasper, Maren; Walscheid, Karoline; Koch, Jörg M; Müther, Philipp S; Kirchhof, Bernd; Heiligenhaus, Arnd; Heinz, Carsten

2018-01-01

Patients with juvenile idiopathic arthritis often develop chronic anterior uveitis (JIAU). JIAU patients possess a particularly high risk for developing secondary glaucoma when inflammatory inactivity has been achieved. By using multiplex bead assay analysis, we assessed levels of pro- and anti-inflammatory cytokines, chemokines, or metalloproteinases in the aqueous humor (AH) of patients with clinically inactive JIAU with (JIAUwG) or without secondary glaucoma (JIAUwoG), or from patients with senile cataract as controls. Laser-flare photometry analysis prior to surgery showed no significant differences between JIAUwG or JIAUwoG. Compared with the control group, levels of interleukin-8, matrix metalloproteinase-2, -3, -9, serum amyloid A (SAA), transforming growth factor beta-1, -2, -3 (TGFβ-1, -2, -3), and tumor necrosis factor-alpha in the AH were significantly higher in patients with clinically inactive JIAUwG or JIAUwoG. Samples from JIAwoG patients displayed significantly higher levels of SAA ( P  < 0.0116) than JIAUwG patients. JIAUwG patients showed an increased level of TGFβ-2 in AH samples compared with JIAUwoG ( P  < 0.0009). These molecules may contribute to the clinical development of glaucoma in patients with JIAU.

A Crossover Trial Evaluating an Educational-Behavioral Joint Protection Programme for People with Rheumatoid Arthritis.

ERIC Educational Resources Information Center

Hammond, A.; Lincoln, N.; Sutcliffe, L.

1999-01-01

Joint protection, a self-management technique taught to people with rheumatoid arthritis, was used in a group education program. A crossover trial (N=35) was conducted. No significant changes in measures of pain, functional disability, grip strength, self-efficacy or helplessness occurred post-education, although this may have been due to the…

Intra-articular glucocorticoid injections in patients with juvenile idiopathic arthritis in a Singapore hospital.

PubMed

Leow, Olivia Min Yi; Lim, Lee Kean; Ooi, Pei Ling; Shek, Lynette Pei Chi; Ang, Elizabeth You Ning; Son, Mary Beth

2014-05-01

This study aimed to evaluate the efficacy and safety of intra-articular glucocorticoid (IAG) injections in our institution in children with juvenile idiopathic arthritis (JIA). This is a retrospective assessment of IAG injections performed by the Department of Paediatrics, National University Hospital, Singapore, from October 2009 to October 2011. A total of 26 procedures were evaluated for efficacy, considering parameters such as clinical response, changes in systemic medication, length of time between repeat injections, safety, consent-taking, pre- and post-procedural advice, compliance with aseptic technique, and post-procedural complications. A total of 26 IAG injections of triamcinolone hexacetonide were administered over 17 occasions (i.e. patient encounters) to ten patients with JIA during the study period. After the injections, clinical scoring by a paediatric rheumatologist showed overall improvement by an average of 2.62 points out of 15. Besides six patient encounters that had an increase in systemic medication on the day of the injection, five required an increase within six months post injection, two required no adjustments, and one resulted in a decrease in medications. In all, 21 injections did not require subsequent injections. The mean interval between repeat injections was 7.8 months. Cutaneous side effects were noted in three anatomically difficult joints. Medical documentation with regard to patient progress was found to be lacking. As per the recommendations of the American College of Rheumatology, we safely used IAG injections as the first-line therapy in our group of patients with oligoarticular JIA, and/or as an adjunct to systemic therapy in our patients with JIA.

The relationship between physical activity levels and pain in children with juvenile idiopathic arthritis.

PubMed

Limenis, Elizaveta; Grosbein, Haddas A; Feldman, Brian M

2014-02-01

Pain and reduced physical activity levels are common in children with juvenile idiopathic arthritis (JIA). Currently, there is no consensus about the role of physical activity in managing pain in JIA. The purpose of our study was to assess the relationship between physical activity level and pain in children ages 11 to 18 years with JIA. A random sample of 50 patients with JIA were approached by mailed questionnaires. Physical activity was determined using the Physical Activity Questionnaire (PAQ). Pain measures included the Numerical Rating Scale (pain severity), SUPER-KIDZ body diagram (number of painful areas), and the Child Activities Limitations Inventory-21 (pain interference). Generalized linear models were used to assess the relationship between physical activity and pain, as well as the roles of sex and age. The response rate was 84%. Thirty-four respondents completed the questionnaire package. The median age was 15 years. The mean PAQ score was 2.16/5. Physical activity declines with increasing age in youth with JIA (r = 0.53, p = 0.0014). Lower physical activity is associated with greater pain interference (r = 0.39, p = 0.0217) and more severe pain (r = 0.35, p = 0.0422). Children with JIA report significantly less activity than healthy children based on PAQ scores, with physical activity declining throughout adolescence. Physical activity is inversely related to pain interference and severity in children with JIA. Our findings suggest that physical activity interventions may play an important role in the management of pain in JIA.

A Novel Mobile App and Population Management System to Manage Rheumatoid Arthritis Flares: Protocol for a Randomized Controlled Trial

PubMed Central

Wang, Penny; Luo, Dee; Lu, Fengxin; Elias, Josephine S; Landman, Adam B; Michaud, Kaleb D

2018-01-01

Background Rheumatoid arthritis flares have a profound effect on patients, causing pain and disability. However, flares often occur between regularly scheduled health care provider visits and are, therefore, difficult to monitor and manage. We sought to develop a mobile phone app combined with a population management system to help track RA flares between visits. Objective The objective of this study is to implement the mobile app plus the population management system to monitor rheumatoid arthritis disease activity between scheduled health care provider visits over a period of 6 months. Methods This is a randomized controlled trial that lasts for 6 months for each participant. We aim to recruit 190 patients, randomized 50:50 to the intervention group versus the control group. The intervention group will be assigned the mobile app and be prompted to answer daily questionnaires sent to their mobile devices. Both groups will be assigned a population manager, who will communicate with the participants via telephone at 6 weeks and 18 weeks. The population manager will also communicate with the participants in the intervention group if their responses indicate a sustained increase in rheumatoid arthritis disease activity. To assess patient satisfaction, the primary outcomes will be scores on the Treatment Satisfaction Questionnaire for Medication as well as the Perceived Efficacy in Patient-Physician Interactions questionnaire at 6 months. To determine the effect of the mobile app on rheumatoid arthritis disease activity, the primary outcome will be the Clinical Disease Activity Index at 6 months. Results The trial started in November 2016, and an estimated 2.5 years will be necessary to complete the study. Study results are expected to be published by the end of 2019. Conclusions The completion of this study will provide important data regarding the following: (1) the assessment of validated outcome measures to assess rheumatoid arthritis disease activity with a mobile

Impact of Antiinflammatory Treatment on the Onset of Uveitis in Juvenile Idiopathic Arthritis: Longitudinal Analysis From a Nationwide Pediatric Rheumatology Database

PubMed Central

Schenck, Sandra; Niewerth, Martina; Heiligenhaus, Arnd; Minden, Kirsten; Klotsche, Jens

2015-01-01

Objective Based on a nationwide database, this study analyzed the influence of methotrexate (MTX), tumor necrosis factor (TNF) inhibitors, and a combination of the 2 medications on uveitis occurrence in juvenile idiopathic arthritis (JIA) patients. Methods Data from the National Paediatric Rheumatological Database in Germany were used in this study. Between 2002 and 2013, data from JIA patients were annually documented at the participating pediatric rheumatologic sites. Patients with a JIA disease duration of <12 months at initial documentation and ≥2 years of followup were included in this study. The impact of antiinflammatory treatment on the occurrence of uveitis was evaluated by discrete‐time survival analysis. Results A total of 3,512 JIA patients (mean ± SD age 8.3 ± 4.8 years, 65.7% female, 53.2% antinuclear antibody positive, and mean ± SD age at arthritis onset 7.8 ± 4.8 years) fulfilled the inclusion criteria. Mean ± SD total followup time was 3.6 ± 2.4 years. Uveitis developed in a total of 180 patients (5.1%) within 1 year after arthritis onset. Uveitis onset after the first year was observed in another 251 patients (7.1%). Disease‐modifying antirheumatic drug (DMARD) treatment in the year before uveitis onset significantly reduced the risk for uveitis as follows: MTX: hazard ratio (HR) 0.63, P = 0.022; TNF inhibitors: HR 0.56, P < 0.001; and a combination of the 2 medications: HR 0.10, P < 0.001. Patients treated with MTX within the first year of JIA had an even a lower uveitis risk (HR 0.29, P < 0.001). Conclusion The use of DMARDs in JIA patients significantly reduced the risk for uveitis onset. Early MTX use within the first year of disease and the combination of MTX with a TNF inhibitor had the highest protective effect. PMID:26212111

Effects of Juvenile Idiopathic Arthritis on Kinematics and Kinetics of the Lower Extremities Call for Consequences in Physical Activities Recommendations

PubMed Central

Hartmann, M.; Kreuzpointner, F.; Haefner, R.; Michels, H.; Schwirtz, A.; Haas, J. P.

2010-01-01

Juvenile idiopathic arthritis (JIA) patients (n = 36) with symmetrical polyarticular joint involvement of the lower extremities and healthy controls (n = 20) were compared concerning differences in kinematic, kinetic, and spatio-temporal parameters with 3D gait analysis. The aims of this study were to quantify the differences in gait between JIA patients and healthy controls and to provide data for more detailed sport activities recommendations. JIA-patients showed reduced walking speed and step length, strongly anterior tilted pelvis, reduced maximum hip extension, reduced knee extension during single support phase and reduced plantar flexion in push off. Additionally the roll-off procedure of the foot was slightly decelerated. The reduced push off motion in the ankle was confirmed by lower peaks in ankle moment and power. The gait of JIA-patients can be explained as a crouch-like gait with hyperflexion in hip and knee joints and less plantar flexion in the ankle. A preventive mobility workout would be recommendable to reduce these restrictions in the future. Advisable are sports with emphasis on extension in hip, knee, and ankle plantar flexion. PMID:20862334

Randomized clinical trials as reflexive-interpretative process in patients with rheumatoid arthritis: a qualitative study.

PubMed

de Jorge, Mercedes; Parra, Sonia; de la Torre-Aboki, Jenny; Herrero-Beaumont, Gabriel

2015-08-01

Patients in randomized clinical trials have to adapt themselves to a restricted language to capture the necessary information to determine the safety and efficacy of a new treatment. The aim of this study was to explore the experience of patients with rheumatoid arthritis after completing their participation in a biologic therapy randomized clinical trial for a period of 3 years. A qualitative approach was used. The information was collected using 15 semi-structured interviews of patients with rheumatoid arthritis. Data collection was guided by the emergent analysis until no more relevant variations in the categories were found. The data were analysed using the grounded theory method. The objective of the patients when entering the study was to improve their quality of life by initiating the treatment. However, the experience changed the significance of the illness as they acquired skills and practical knowledge related to the management of their disease. The category "Interactional Empowerment" emerged as core category, as it represented the participative experience in a clinical trial. The process integrates the follow categories: "weight of systematisation", "working together", and the significance of the experience: "the duties". Simultaneously these categories evolved. The clinical trial monitoring activities enabled patients to engage in a reflexive-interpretative mechanism that transformed the emotional and symbolic significance of their disease and improved the empowerment of the patient. A better communicative strategy with the health professionals, the relatives of the patients, and the community was also achieved.

Sensitivity Analyses of the Change in FVC in a Phase 3 Trial of Pirfenidone for Idiopathic Pulmonary Fibrosis

PubMed Central

Bradford, Williamson Z.; Fagan, Elizabeth A.; Glaspole, Ian; Glassberg, Marilyn K.; Glasscock, Kenneth F.; King, Talmadge E.; Lancaster, Lisa H.; Nathan, Steven D.; Pereira, Carlos A.; Sahn, Steven A.; Swigris, Jeffrey J.; Noble, Paul W.

2015-01-01

BACKGROUND: FVC outcomes in clinical trials on idiopathic pulmonary fibrosis (IPF) can be substantially influenced by the analytic methodology and the handling of missing data. We conducted a series of sensitivity analyses to assess the robustness of the statistical finding and the stability of the estimate of the magnitude of treatment effect on the primary end point of FVC change in a phase 3 trial evaluating pirfenidone in adults with IPF. METHODS: Source data included all 555 study participants randomized to treatment with pirfenidone or placebo in the Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis (ASCEND) study. Sensitivity analyses were conducted to assess whether alternative statistical tests and methods for handling missing data influenced the observed magnitude of treatment effect on the primary end point of change from baseline to week 52 in FVC. RESULTS: The distribution of FVC change at week 52 was systematically different between the two treatment groups and favored pirfenidone in each analysis. The method used to impute missing data due to death had a marked effect on the magnitude of change in FVC in both treatment groups; however, the magnitude of treatment benefit was generally consistent on a relative basis, with an approximate 50% reduction in FVC decline observed in the pirfenidone group in each analysis. CONCLUSIONS: Our results confirm the robustness of the statistical finding on the primary end point of change in FVC in the ASCEND trial and corroborate the estimated magnitude of the pirfenidone treatment effect in patients with IPF. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01366209; URL: www.clinicaltrials.gov PMID:25856121

The effect of genotype on methotrexate polyglutamate variability in juvenile idiopathic arthritis and association with drug response.

PubMed

Becker, Mara L; Gaedigk, Roger; van Haandel, Leon; Thomas, Bradley; Lasky, Andrew; Hoeltzel, Mark; Dai, Hongying; Stobaugh, John; Leeder, J Steven

2011-01-01

The response to and toxicity of methotrexate (MTX) are unpredictable in patients with juvenile idiopathic arthritis (JIA). Intracellular polyglutamation of MTX, assessed by measuring concentrations of MTX polyglutamates (MTXGlu), has been demonstrated to be a promising predictor of drug response. Therefore, this study was aimed at investigating the genetic predictors of MTXGlu variability and associations between MTXGlu and drug response in JIA. The study was designed as a single-center cross-sectional analysis of patients with JIA who were receiving stable doses of MTX at a tertiary care children's hospital. After informed consent was obtained from the 104 patients with JIA, blood was withdrawn during routine MTX-screening laboratory testing. Clinical data were collected by chart review. Genotyping for 34 single-nucleotide polymorphisms (SNPs) in 18 genes within the MTX metabolic pathway was performed. An ion-pair chromatographic procedure with mass spectrometric detection was used to measure MTXGlu1-7. Analysis and genotyping of MTXGlu was completed in the 104 patients. K-means clustering resulted in 3 distinct patterns of MTX polyglutamation. Cluster 1 had low red blood cell (RBC) MTXGlu concentrations, cluster 2 had moderately high RBC MTXGlu1+2 concentrations, and cluster 3 had high concentrations of MTXGlu, specifically MTXGlu3-5. SNPs in the purine and pyrimidine synthesis pathways, as well as the adenosine pathway, were significantly associated with cluster subtype. The cluster with high concentrations of MTXGlu3-5 was associated with elevated liver enzyme levels on liver function tests (LFTs), and there were higher concentrations of MTXGlu3-5 in children who reported gastrointestinal side effects and had abnormal findings on LFTs. No association was noted between MTXGlu and active arthritis. MTXGlu remains a potentially useful tool for determining outcomes in patients with JIA being treated with MTX. The genetic predictors of MTXGlu variability may also

Fine-mapping the MHC locus in juvenile idiopathic arthritis (JIA) reveals genetic heterogeneity corresponding to distinct adult inflammatory arthritic diseases

PubMed Central

Hinks, A; Cobb, J; Ainsworth, H C; Marion, M C; Comeau, M E; Sudman, M; Han, B; Becker, M L; Bohnsack, J F; de Bakker, P I W; Haas, J P; Hazen, M; Lovell, D J; Nigrovic, P A; Nordal, E; Punnaro, M; Rosenberg, A M; Rygg, M; Wise, C A; Videm, V; Wedderburn, L R; Yarwood, A; Yeung, R S M; Prahalad, S; Langefeld, C D; Raychaudhuri, S; Thompson, S D; Thomson, W

2017-01-01

Objectives Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases, comprising seven categories. Genetic data could potentially be used to help redefine JIA categories and improve the current classification system. The human leucocyte antigen (HLA) region is strongly associated with JIA. Fine-mapping of the region was performed to look for similarities and differences in HLA associations between the JIA categories and define correspondences with adult inflammatory arthritides. Methods Dense genotype data from the HLA region, from the Immunochip array for 5043 JIA cases and 14 390 controls, were used to impute single-nucleotide polymorphisms, HLA classical alleles and amino acids. Bivariate analysis was performed to investigate genetic correlation between the JIA categories. Conditional analysis was used to identify additional effects within the region. Comparison of the findings with those in adult inflammatory arthritic diseases was performed. Results We identified category-specific associations and have demonstrated for the first time that rheumatoid factor (RF)-negative polyarticular JIA and oligoarticular JIA are genetically similar in their HLA associations. We also observe that each JIA category potentially has an adult counterpart. The RF-positive polyarthritis association at HLA-DRB1 amino acid at position 13 mirrors the association in adult seropositive rheumatoid arthritis (RA). Interestingly, the combined oligoarthritis and RF-negative polyarthritis dataset shares the same association with adult seronegative RA. Conclusions The findings suggest the value of using genetic data in helping to classify the categories of this heterogeneous disease. Mapping JIA categories to adult counterparts could enable shared knowledge of disease pathogenesis and aetiology and facilitate transition from paediatric to adult services. PMID:27998952

Sensitivity Analyses of the Change in FVC in a Phase 3 Trial of Pirfenidone for Idiopathic Pulmonary Fibrosis.

PubMed

Lederer, David J; Bradford, Williamson Z; Fagan, Elizabeth A; Glaspole, Ian; Glassberg, Marilyn K; Glasscock, Kenneth F; Kardatzke, David; King, Talmadge E; Lancaster, Lisa H; Nathan, Steven D; Pereira, Carlos A; Sahn, Steven A; Swigris, Jeffrey J; Noble, Paul W

2015-07-01

FVC outcomes in clinical trials on idiopathic pulmonary fibrosis (IPF) can be substantially influenced by the analytic methodology and the handling of missing data. We conducted a series of sensitivity analyses to assess the robustness of the statistical finding and the stability of the estimate of the magnitude of treatment effect on the primary end point of FVC change in a phase 3 trial evaluating pirfenidone in adults with IPF. Source data included all 555 study participants randomized to treatment with pirfenidone or placebo in the Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis (ASCEND) study. Sensitivity analyses were conducted to assess whether alternative statistical tests and methods for handling missing data influenced the observed magnitude of treatment effect on the primary end point of change from baseline to week 52 in FVC. The distribution of FVC change at week 52 was systematically different between the two treatment groups and favored pirfenidone in each analysis. The method used to impute missing data due to death had a marked effect on the magnitude of change in FVC in both treatment groups; however, the magnitude of treatment benefit was generally consistent on a relative basis, with an approximate 50% reduction in FVC decline observed in the pirfenidone group in each analysis. Our results confirm the robustness of the statistical finding on the primary end point of change in FVC in the ASCEND trial and corroborate the estimated magnitude of the pirfenidone treatment effect in patients with IPF. ClinicalTrials.gov; No.: NCT01366209; URL: www.clinicaltrials.gov.

Statin Therapy and Outcomes in Trials of Nintedanib in Idiopathic Pulmonary Fibrosis.

PubMed

Kreuter, Michael; Costabel, Ulrich; Richeldi, Luca; Cottin, Vincent; Wijsenbeek, Marlies; Bonella, Francesco; Bendstrup, Elisabeth; Maher, Toby M; Wachtlin, Daniel; Stowasser, Susanne; Kolb, Martin

Cardiovascular comorbidities are frequent in patients with idiopathic pulmonary fibrosis (IPF), and many patients with IPF receive treatment with statins to reduce cardiovascular risk. We investigated whether statin use at baseline was associated with differences in disease progression in placebo-treated patients or influenced the treatment effect of nintedanib in the INPULSIS® trials. Post-hoc subgroup analyses of patients receiving versus not receiving statins at baseline using pooled data from the INPULSIS® trials. At baseline, 312 patients received statins and 749 did not. The annual rates of decline in forced vital capacity (FVC) in patients treated with nintedanib and placebo, respectively, were -78.9 and -187.6 mL/year in patients who received statins at baseline, and -127.9 and -237.9 mL/year in patients who did not. The effect of nintedanib was consistent across subgroups (p = 0.9590). In the INPULSIS® trials, there was a numerically lower FVC decline in placebo-treated patients with IPF who received statins at baseline versus those who did not. Use of statins at baseline did not influence the treatment effect of nintedanib. Prospective data are needed to assess the impact of statins on the course of IPF. © 2018 S. Karger AG, Basel.

The dental attitudes, knowledge and health practices of patients with Juvenile Idiopathic Arthritis.

PubMed

Waterhouse, P J; Thomason, J M; Fitzgerald, J F; Foster, H E; Steen, I N; Welbury, R R

2005-12-01

To investigate the dental attitudes, knowledge and dental health practices of children and adults with a previous diagnosis of Juvenile Idiopathic Arthritis (JIA). A self-completion questionnaire. Ninety-one children and 82 adults with JIA were age and gender matched with 152 healthy controls. For those below the age of 16 years, the parents' attitude, knowledge and dental health practices were investigated by the questionnaire. The adult subjects and controls completed an identical questionnaire assessing their own attitude, knowledge and dental health practices. Response rates of 84% and 75% were achieved for the subject and controls respectively. Both groups responded similarly to questions assessing perception of different medical conditions. The majority of respondents thought leukaemia was a very serious condition. Twenty-seven percent of subjects and 34% of controls felt dental decay was "slightly or not serious". Ninety percent of subjects and 93% of controls knew having sweet snacks during the day would harm teeth, but fewer were sure that eating sweet foods at mealtimes only would help reduce decay. The majority of respondents (63% and 56% respectively) did not know whether children should receive fluoride tablets but the majority of subjects in both groups had attended a dentist within the last year. Descriptive analyses and chi-squared analysis were undertaken. A p-value of < or =0.01 was taken as strong evidence of a difference between groups. The perception of health and illness by both groups was appropriate. The questions investigating dental knowledge revealed understanding of the basic messages of prevention of dental disease, but finer detail appeared less well understood. Responses concerning dental health confirmed positive attitudes towards good dental health habits. The benefits of brushing with fluoride toothpaste were known, and the majority toothbrushed daily and received dental care within the previous year.

Tofacitinib in psoriatic arthritis.

PubMed

Wang, Ting-Shun; Tsai, Tsen-Fang

2017-11-01

Psoriatic arthritis is a heterogeneous disease that has been difficult to manage until the recent advent of biologics. However, there are still unmet medical needs for newer agents. Tofacitinib is a Janus family of kinases inhibitor approved for treating rheumatoid arthritis in many countries and psoriasis in Russia. We reviewed the evidences of tofacitinib in psoriatic arthritis treatment. The efficacy and safety profiles result from Phase III clinical trials (OPAL BROADEN and OPAL BEYOND) and one open-label extension study (OPAL BALANCE). Both tofacitinib 5 or 10 mg twice a day were superior to placebo for American College of Rheumatology 20% improvement criteria response at 3 months and showed significant improvement of skin, enthesitis and dactylitis. Tofacitinib is a promising treatment option for psoriatic arthritis.

Double-blind trial of recombinant gamma-interferon versus placebo in the treatment of rheumatoid arthritis. 1989.

PubMed

Cannon, Grant W; Pincus, Seth H; Emkey, Ronald D; Denes, Alex; Cohen, Selwyn A; Wolfe, Frederick; Saway, P Anthony; Jaffer, Adrian M; Weaver, Arthur L; Cogen, Lewis; Schindler, John D

2008-02-01

One hundred five patients were enrolled in a 12-week, randomized, prospective, double-blind, placebo-controlled trial of recombinant human gamma-interferon (rHu gamma-IFN) for the treatment of rheumatoid arthritis. Fifty-four patients received rHu gamma-IFN and 51 received placebo. Forty-two patients in each group completed the 12-week trial. Some clinical improvement occurred in both groups of patients. Although the improvement with rHu gamma-IFN was greater than that with placebo, the differences were generally not statistically significant.

Intra-articular glucocorticoid injections in patients with juvenile idiopathic arthritis in a Singapore hospital

PubMed Central

Leow, Olivia Min Yi; Lim, Lee Kean; Ooi, Pei Ling; Shek, Lynette Pei Chi; Ang, Elizabeth You Ning; Son, Mary Beth

2014-01-01

INTRODUCTION This study aimed to evaluate the efficacy and safety of intra-articular glucocorticoid (IAG) injections in our institution in children with juvenile idiopathic arthritis (JIA). METHODS This is a retrospective assessment of IAG injections performed by the Department of Paediatrics, National University Hospital, Singapore, from October 2009 to October 2011. A total of 26 procedures were evaluated for efficacy, considering parameters such as clinical response, changes in systemic medication, length of time between repeat injections, safety, consent-taking, pre- and post-procedural advice, compliance with aseptic technique, and post-procedural complications. RESULTS A total of 26 IAG injections of triamcinolone hexacetonide were administered over 17 occasions (i.e. patient encounters) to ten patients with JIA during the study period. After the injections, clinical scoring by a paediatric rheumatologist showed overall improvement by an average of 2.62 points out of 15. Besides six patient encounters that had an increase in systemic medication on the day of the injection, five required an increase within six months post injection, two required no adjustments, and one resulted in a decrease in medications. In all, 21 injections did not require subsequent injections. The mean interval between repeat injections was 7.8 months. Cutaneous side effects were noted in three anatomically difficult joints. Medical documentation with regard to patient progress was found to be lacking. CONCLUSION As per the recommendations of the American College of Rheumatology, we safely used IAG injections as the first-line therapy in our group of patients with oligoarticular JIA, and/or as an adjunct to systemic therapy in our patients with JIA. PMID:24862747

A Patient-Specific Foot Model for the Estimate of Ankle Joint Forces in Patients with Juvenile Idiopathic Arthritis.

PubMed

Prinold, Joe A I; Mazzà, Claudia; Di Marco, Roberto; Hannah, Iain; Malattia, Clara; Magni-Manzoni, Silvia; Petrarca, Maurizio; Ronchetti, Anna B; Tanturri de Horatio, Laura; van Dijkhuizen, E H Pieter; Wesarg, Stefan; Viceconti, Marco

2016-01-01

Juvenile idiopathic arthritis (JIA) is the leading cause of childhood disability from a musculoskeletal disorder. It generally affects large joints such as the knee and the ankle, often causing structural damage. Different factors contribute to the damage onset, including altered joint loading and other mechanical factors, associated with pain and inflammation. The prediction of patients' joint loading can hence be a valuable tool in understanding the disease mechanisms involved in structural damage progression. A number of lower-limb musculoskeletal models have been proposed to analyse the hip and knee joints, but juvenile models of the foot are still lacking. This paper presents a modelling pipeline that allows the creation of juvenile patient-specific models starting from lower limb kinematics and foot and ankle MRI data. This pipeline has been applied to data from three children with JIA and the importance of patient-specific parameters and modelling assumptions has been tested in a sensitivity analysis focused on the variation of the joint reaction forces. This analysis highlighted the criticality of patient-specific definition of the ankle joint axes and location of the Achilles tendon insertions. Patient-specific detection of the Tibialis Anterior, Tibialis Posterior, and Peroneus Longus origins and insertions were also shown to be important.

A survey of national and multi-national registries and cohort studies in juvenile idiopathic arthritis: challenges and opportunities.

PubMed

Beukelman, Timothy; Anink, Janneke; Berntson, Lillemor; Duffy, Ciaran; Ellis, Justine A; Glerup, Mia; Guzman, Jaime; Horneff, Gerd; Kearsley-Fleet, Lianne; Klein, Ariane; Klotsche, Jens; Magnusson, Bo; Minden, Kirsten; Munro, Jane E; Niewerth, Martina; Nordal, Ellen; Ruperto, Nicolino; Santos, Maria Jose; Schanberg, Laura E; Thomson, Wendy; van Suijlekom-Smit, Lisette; Wulffraat, Nico; Hyrich, Kimme

2017-04-19

To characterize the existing national and multi-national registries and cohort studies in juvenile idiopathic arthritis (JIA) and identify differences as well as areas of potential future collaboration. We surveyed investigators from North America, Europe, and Australia about existing JIA cohort studies and registries. We excluded cross-sectional studies. We captured information about study design, duration, location, inclusion criteria, data elements and collection methods. We received survey results from 18 studies, including 11 national and 7 multi-national studies representing 37 countries in total. Study designs included inception cohorts, prevalent disease cohorts, and new treatment cohorts (several of which contribute to pharmacosurveillance activities). Despite numerous differences, the data elements collected across the studies was quite similar, with most studies collecting at least 5 of the 6 American College of Rheumatology core set variables and the data needed to calculate the 3-variable clinical juvenile disease activity score. Most studies were collecting medication initiation and discontinuation dates and were attempting to capture serious adverse events. There is a wide-range of large, ongoing JIA registries and cohort studies around the world. Our survey results indicate significant potential for future collaborative work using data from different studies and both combined and comparative analyses.

"Employment and arthritis: making it work" a randomized controlled trial evaluating an online program to help people with inflammatory arthritis maintain employment (study protocol).

PubMed

Carruthers, Erin C; Rogers, Pamela; Backman, Catherine L; Goldsmith, Charles H; Gignac, Monique A; Marra, Carlo; Village, Judy; Li, Linda C; Esdaile, John M; Lacaille, Diane

2014-07-21

Arthritis and musculoskeletal conditions are the leading cause of long-term work disability (WD), an outcome with a major impact on quality of life and a high cost to society. The importance of decreased at-work productivity has also recently been recognized. Despite the importance of these problems, few interventions have been developed to reduce the impact of arthritis on employment. We have developed a novel intervention called "Making It Work", a program to help people with inflammatory arthritis (IA) deal with employment issues, prevent WD and improve at-work productivity. After favorable results in a proof-of-concept study, we converted the program to a web-based format for broader dissemination and improved accessibility. The objectives of this study are: 1) to evaluate in a randomized controlled trial (RCT) the effectiveness of the program at preventing work cessation and improving at-work productivity; 2) to perform a cost-utility analysis of the intervention. 526 participants with IA will be recruited from British Columbia, Alberta, and Ontario in Canada. The intervention consists of a) 5 online group sessions; b) 5 web-based e-learning modules; c) consultations with an occupational therapist for an ergonomic work assessment and a vocational rehabilitation counselor. Questionnaires will be administered online at baseline and every 6 months to collect information about demographics, disease measures, costs, work-related risk factors for WD, quality of life, and work outcomes. Primary outcomes include at-work productivity and time to work cessation of > 6 months for any reason. Secondary outcomes include temporary work cessation, number of days missed from work per year, reduction in hours worked per week, quality adjusted life year for the cost utility analysis, and changes from baseline in employment risk factors. Analysis of Variance will evaluate the intervention's effect on at-work productivity, and multivariable Cox regression models will

A 6-month, multicenter, open-label study of fixed dose naproxen/esomeprazole in adolescent patients with juvenile idiopathic arthritis.

PubMed

Lovell, Daniel J; Dare, Jason A; Francis-Sedlak, Megan; Ball, Julie; LaMoreaux, Brian D; Von Scheven, Emily; Reinhardt, Adam; Jerath, Rita; Alpan, Oral; Gupta, Ramesh; Goldsmith, Donald; Zeft, Andrew; Naddaf, Henry; Gottlieb, Beth; Jung, Lawrence; Holt, Robert J

2018-06-26

Juvenile idiopathic arthritis (JIA) is an inflammatory arthritis of unknown etiology, which lasts for greater than 6 weeks with onset before 16 years of age. JIA is the most common chronic rheumatic disease in children. NSAIDs have been the mainstay of initial management with naproxen (NAP) being commonly used, but they may cause serious side effects such as gastric ulcers which can be reduced by concomitant administration of proton pump inhibitors, such as esomeprazole (ESO). Primary objective was to evaluate the safety and tolerability of 3 fixed doses of NAP/ESO in JIA patients aged 12 to 16 years. Forty-six children and adolescents with JIA by International League of Associations for Rheumatology criteria, mean age of 13.6 years, from 18 US sites were prospectively enrolled over 2 years and followed for up to 6 months. Doses of the NAP/ESO fixed combination were based on baseline weight. The exploratory efficacy outcome was assessed with the ACR Pediatric-30, - 50, - 70, - 90 Response and the Childhood Health Assessment Questionnaire (CHAQ) discomfort and functional scores at months 1, 3, and 6 as change from baseline. Occurrence and causality were assessed for treatment emergent AEs (TEAEs) and discontinuations were monitored monthly. Forty-six patients received at least 1 dose of naproxen/esomeprazole and 36 completed the trial. Thirty-seven (80.4%) had at least 1 treatment emergent adverse event (TEAE) and, with the exception of 2 events in one patient, all of the TEAEs were mild or moderate. Frequent TEAEs (≥5% of patients) were upper respiratory tract and gastrointestinal related. Eleven (23.9%) had at least 1 TEAE considered to be related to study drug. Four patients (8.7%) discontinued due to a TEAE with one of these being the only serious AE reported, acute hepatitis. Mean number of active joints at baseline was 3.1. Improvement in JIA signs and symptoms occurred at most assessments and by month 6, the percentage of patients with an ACR

Personalized Risk Estimator for Rheumatoid Arthritis (PRE-RA) Family Study: Rationale and design for a randomized controlled trial evaluating rheumatoid arthritis risk education to first-degree relatives

PubMed Central

Sparks, Jeffrey A.; Iversen, Maura D.; Kroouze, Rachel Miller; Mahmoud, Taysir G.; Triedman, Nellie A.; Kalia, Sarah S.; Atkinson, Michael L.; Lu, Bing; Deane, Kevin D.; Costenbader, Karen H.; Green, Robert C.; Karlson, Elizabeth W.

2014-01-01

We present the rationale, design features, and protocol of the Personalized Risk Estimator for Rheumatoid Arthritis (PRE-RA) Family Study (ClinicalTrials.gov NCT02046005). The PRE-RA Family Study is an NIH-funded prospective, randomized controlled trial designed to compare the willingness to change behaviors in first-degree relatives of rheumatoid arthritis (RA) patients without RA after exposure to RA risk educational programs. Consented subjects are randomized to receive education concerning their personalized RA risk based on demographics, RA-associated behaviors, genetics and biomarkers or to receive standard RA information. Four behavioral factors associated with RA risk were identified from prior studies for inclusion in the risk estimate: cigarette smoking, excess body weight, poor oral health, and low fish intake. Personalized RA risk information is presented through an online tool that collects data on an individual's specific age, gender, family history, and risk-related behaviors; presents genetic and biomarker results; displays relative and absolute risk of RA; and provides personalized feedback and education. The trial outcomes will be changes in willingness to alter behaviors from baseline to 6 weeks, 6 months, and 12 months in the three intervention groups. The design and execution of this trial that targets a special population at risk for RA, while incorporating varied risk factors into a single risk tool, offer distinct challenges. We provide the theoretical rationale for the PRE-RA Family Study and highlight particular design features of this trial that utilize personalized risk education as an intervention. PMID:25151341

Personalized Risk Estimator for Rheumatoid Arthritis (PRE-RA) Family Study: rationale and design for a randomized controlled trial evaluating rheumatoid arthritis risk education to first-degree relatives.

PubMed

Sparks, Jeffrey A; Iversen, Maura D; Miller Kroouze, Rachel; Mahmoud, Taysir G; Triedman, Nellie A; Kalia, Sarah S; Atkinson, Michael L; Lu, Bing; Deane, Kevin D; Costenbader, Karen H; Green, Robert C; Karlson, Elizabeth W

2014-09-01

We present the rationale, design features, and protocol of the Personalized Risk Estimator for Rheumatoid Arthritis (PRE-RA) Family Study (ClinicalTrials.gov NCT02046005). The PRE-RA Family Study is an NIH-funded prospective, randomized controlled trial designed to compare the willingness to change behaviors in first-degree relatives of rheumatoid arthritis (RA) patients without RA after exposure to RA risk educational programs. Consented subjects are randomized to receive education concerning their personalized RA risk based on demographics, RA-associated behaviors, genetics, and biomarkers or to receive standard RA information. Four behavioral factors associated with RA risk were identified from prior studies for inclusion in the risk estimate: cigarette smoking, excess body weight, poor oral health, and low fish intake. Personalized RA risk information is presented through an online tool that collects data on an individual's specific age, gender, family history, and risk-related behaviors; presents genetic and biomarker results; displays relative and absolute risk of RA; and provides personalized feedback and education. The trial outcomes will be changes in willingness to alter behaviors from baseline to 6 weeks, 6 months, and 12 months in the three intervention groups. The design and the execution of this trial that targets a special population at risk for RA, while incorporating varied risk factors into a single risk tool, offer distinct challenges. We provide the theoretical rationale for the PRE-RA Family Study and highlight particular design features of this trial that utilize personalized risk education as an intervention. Copyright © 2014 Elsevier Inc. All rights reserved.

Surfing for juvenile idiopathic arthritis: perspectives on quality and content of information on the Internet.

PubMed

Stinson, Jennifer N; Tucker, Lori; Huber, Adam; Harris, Heather; Lin, Carmen; Cohen, Lindsay; Gill, Navreet; Lukas-Bretzler, Jacqueline; Proulx, Laurie; Prowten, David

2009-08-01

To determine the quality and content of English language Internet information about juvenile idiopathic arthritis (JIA) from the perspectives of consumers and healthcare professionals. Key words relevant to JIA were searched across 10 search engines. Quality of information was appraised independently by 2 health professionals, 1 young adult with JIA, and a parent using the DISCERN tool. Concordance of the website content (i.e., accuracy and completeness) with available evidence about the management of JIA was determined. Readability was determined using Flesch-Kincaid grade level and Reading Ease Score. Out of the 3000 Web pages accessed, only 58 unique sites met the inclusion criteria. Of these sites only 16 had DISCERN scores above 50% (indicating fair quality). These sites were then rated by consumers. Most sites targeted parents and none were specifically developed for youth with JIA. The overall quality of website information was fair, with a mean DISCERN quality rating score of 48.92 out of 75 (+/- 6.56, range 34.0-59.5). Overall completeness of sites was 9.07 out of 16 (+/- 2.28, range 5.25-13.25) and accuracy was 3.09 out of 4 (+/- 0.86, range 2-4), indicating a moderate level of accuracy. Average Flesch-Kincaid grade level and Reading Ease Score were 11.48 (+/- 0.74, range 10.1-12.0) and 36.36 (+/- 10.86, range 6.30-48.1), respectively, indicating that the material was difficult to read. Our study highlights the paucity of high quality Internet health information at an appropriate reading level for youth with JIA and their parents.

Acute hepatitis in three patients with systemic juvenile idiopathic arthritis taking interleukin-1 receptor antagonist.

PubMed

Canna, Scott; Frankovich, Jennifer; Higgins, Gloria; Narkewicz, Michael R; Nash, S Russell; Hollister, J Roger; Soep, Jennifer B; Dragone, Leonard L

2009-12-22

We investigated the etiology of acute hepatitis in three children with systemic Juvenile Idiopathic Arthritis (sJIA) taking Interleukin-1 receptor antagonist (IL1RA). Laboratory and clinical data for three children with sJIA diagnosed at ages 13 months to 8 years who developed acute hepatitis during treatment with IL1RA were reviewed for evidence of sJIA flare, infection, macrophage activation syndrome (MAS), malignancy, and drug reaction. In all patients, hepatitis persisted despite cessation of known hepatotoxic drugs and in absence of known infectious triggers, until discontinuation of IL1RA. Liver biopsies had mixed inflammatory infiltrates with associated hepatocellular injury suggestive of an exogenous trigger. At the time of hepatitis, laboratory data and liver biopsies were not characteristic of MAS. In two patients, transaminitis resolved within one week of discontinuing IL1RA, the third improved dramatically in one month. Although sJIA symptoms improved significantly on IL1RA, it appeared that IL1RA contributed to the development of acute hepatitis. Hepatitis possibly occurred as a result of an altered immune response to a typical childhood infection while on IL1RA. Alternatively, hepatitis could have represented an atypical presentation of MAS in patients with sJIA taking IL1RA. Further investigation is warranted to determine how anti-IL1 therapies alter immune responsiveness to exogenous triggers in patients with immune dysfunction such as sJIA. Our patients suggest that close monitoring for hepatic and other toxicities is indicated when treating with IL1RA.

Frequency of radiographic damage and progression in individual joints in children with juvenile idiopathic arthritis.

PubMed

Giancane, Gabriella; Pederzoli, Silvia; Norambuena, Ximena; Ioseliani, Maka; Sato, Juliana; Gallo, Maria Chiara; Negro, Giorgia; Pistorio, Angela; Ruperto, Nicolino; Martini, Alberto; Ravelli, Angelo

2014-01-01

To evaluate the presence and progression of radiographic joint damage, as assessed with the adapted Sharp/van der Heijde score (SHS), in individual joints in the hand and wrist in patients with juvenile idiopathic arthritis (JIA) and to compare progression of damage among different JIA categories. A total of 372 radiographs of both wrists and hands obtained at first observation and at last followup visit (after 1-10 years) in 186 children with polyarticular-course JIA were evaluated. All radiographs were scored using the adapted SHS by 2 independent readers. Radiographic assessment included evaluation of joint space narrowing (JSN) and erosions on baseline and last followup radiographs and of progression of radiographic changes from baseline to last followup radiographs. Both JSN and erosions occurred in all adapted SHS areas. Overall, radiographic damage and progression were more common in the wrist and less common in metacarpophalangeal (MCP) joints. The hamate and capitate areas appeared particularly vulnerable to cartilage loss. Erosions were identified most frequently in the hamate and capitate bones as well as in the second and third metacarpal bases. Patients with extended oligoarthritis were distinctly less susceptible to JSN in hand joints, whereas patients with polyarthritis showed a greater tendency to developing erosions in hand joints. Radiographic joint damage and progression in our patients with JIA were seen most commonly in the wrist and less commonly in MCP joints. The frequency and localization of structural abnormalities differed markedly across disease categories. Copyright © 2014 by the American College of Rheumatology.

Longterm Safety and Efficacy of Adalimumab and Infliximab for Uveitis Associated with Juvenile Idiopathic Arthritis.

PubMed

Cecchin, Vanessa; Zannin, Maria Elisabetta; Ferrari, Daniele; Pontikaki, Irene; Miserocchi, Elisabetta; Paroli, Maria P; Bracaglia, Claudia; Marafon, Denise Pires; Pastore, Serena; Parentin, Fulvio; Simonini, Gabriele; De Libero, Cinzia; Falcini, Fernanda; Petaccia, Antonella; Filocamo, Giovanni; De Marco, Riccardo; La Torre, Francesco; Guerriero, Silvana; Martino, Silvana; Comacchio, Francesco; Muratore, Valentina; Martini, Giorgia; Vittadello, Fabio; Zulian, Francesco

2018-04-15

Anti-TNF-α agents have significantly changed the management of juvenile idiopathic arthritis (JIA). We evaluated the safety and efficacy of adalimumab (ADA) and infliximab (IFX) for the treatment of JIA-associated uveitis in patients treated for ≥ 2 years. Patients with JIA-associated uveitis treated with IFX and ADA were managed by a standardized protocol and data were entered in the ORCHIDEA registry. At baseline, all patients were refractory to standard immunosuppressive treatment or were corticosteroid-dependent. Data recorded every 3 months were uveitis course, number/type of ocular flares and complications, drug-related adverse events (AE), and treatment switch or withdrawal. Data of patients treated for ≥ 2 years were analyzed by descriptive statistics. Up to December 2014, 154 patients with ≥ 24 months followup were included in the study. Fifty-nine patients were treated with IFX and 95 with ADA. Clinical remission, defined as the absence of flares for > 6 months on treatment, was achieved in 69 patients (44.8%), with a better remission rate for ADA (60.0%) as compared to IFX (20.3%; p < 0.001). A significant reduction of flares was observed in all patients without difference between the 2 treatment modalities. The number of new ocular complications decreased in both groups but was lower for ADA (p = 0.015). No serious AE were recorded; 16.4% of patients experienced 35 minor AE and the incidence rate was lower with ADA than with IFX. At the 2-year followup, ADA showed a better efficacy and safety profile than IFX for the treatment of refractory JIA-associated uveitis.

Cost of biologics in the treatment of juvenile idiopathic arthritis: a factor not to be overlooked.

PubMed

Prince, Femke H M; van Suijlekom-Smit, Lisette W A

2013-08-01

Biologics are a promising treatment option for juvenile idiopathic arthritis (JIA) but drug costs are very high compared to conventional treatment. From a socioeconomic view the additional costs of new interventions should be weighed against their incremental health benefits compared to standard care. Therefore we evaluated data on cost-effectiveness of biologics in JIA. We searched Medline, Embase, and The York Centre for Reviews and Dissemination database for relevant literature. Current data show that biologics are reducing direct and indirect healthcare costs if one excludes the costs of the drug itself. The costs of biologics are more than ten times as high as conventional drug treatment. As a result of limited data, no comparison on cost-effectiveness between biologics could be performed. Although data on long-term cost-effectiveness of biologics are lacking, the expectation is that they will be cost-effective in the long-term. The idea behind this is that biologic treatment should be administered to patients that without these drugs would incur high direct and indirect costs due to continuous severe disease resulting in irreversible disabilities. In our opinion the best cost benefit could be gained if these patients receive biologic treatment introduced early in the disease. This is in order to minimize irreversible damage to the joints and minimize need for long-term biologic therapy by early suppression of the disease. To support these hypotheses future research is needed on long-term cost-effectiveness of all biologics used in JIA.

Frequency of auditory involvement and of associated factors in patients with juvenile idiopathic arthritis.

PubMed

Céspedes Cruz, Adriana Ivonne; Méndez Núñez, Myriam; Solís Vallejo, Eunice; Zeferino Cruz, Maritza; Torres Jiménez, Alfonso Ragnar; Ocampo Sánchez, Verónica; Flores Meza, Beatriz; Quintana Ruiz, Norma

2017-09-08

Juvenile idiopathic arthritis (JIA) is a chronic autoimmune disease characterized by the presence of arthritis in children under 16 years of age for more than 6 weeks in the absence of any other known cause. The extra-articular manifestations, especially in the audiovestibular system, are related to the involvement of the joints of the ossicular chain as a result of the inflammatory process in the synovium. Previous clinical studies in pediatric patients have shown conductive or sensorineural hearing loss. The aim of this study was to assess the frequency of hearing impairment and of associated factors in patients with JIA. A prospective, analytical study was conducted from January 2013 to August 2014 in 62 patients with JIA aged between 5 and 15 years. The study was approved by the local ethics committee and parents signed their informed consent. All subjects underwent audiological examination involving otomicroscopy, audiometry, tympanometry, stapedius reflex and test for transient otoacoustic emissions (TOAE); rheumatologic evaluation included joint examination and the application of a measure of functional ability (disability) using the Childhood Health Assessment Questionnaire (CHAQ). Measures of central tendency and of dispersion were used (chi-square for associations and P<.05 for statistical significance). Sixty-two patients were included: 56 girls and 6 boys, mean age 11.9 years and mean disease duration of 3.4 years; 46% had rheumatoid factor (RF)- positive polyarticular JIA, 40% had RF-negative polyarticular JIA, 15% had disease of systemic onset and 3% had oligoarthritis. Active disease was found in 29 patients and 33 were in remission with medication. Of the total of 124 ears evaluated according to the Jerger classification for tympanometry, abnormal findings were observed in 78 that were type As and in 1 that was type Ad, whereas there were 45 type A ears. Hearing loss was disclosed by speech audiometry, rather than by pure tone audiometry. The TOAE

Predictors of Flare Following Etanercept Withdrawal in Patients with Rheumatoid Factor-negative Juvenile Idiopathic Arthritis Who Reached Remission while Taking Medication.

PubMed

Aquilani, Angela; Pires Marafon, Denise; Marasco, Emiliano; Nicolai, Rebecca; Messia, Virginia; Perfetti, Francesca; Magni-Manzoni, Silvia; De Benedetti, Fabrizio

2018-05-01

To evaluate the rate of flare after etanercept (ETN) withdrawal in patients with juvenile idiopathic arthritis (JIA) who attained clinical remission while taking medication, and to identify predictors of flare. Patients were included with oligo- (oJIA) and rheumatoid factor-negative polyarticular JIA (pJIA) who received a first course of ETN for at least 18 months, maintained clinically inactive disease (CID) for at least 6 months during treatment, and were followed for 12 months after ETN withdrawal. Demographic and clinical features were collected at onset, at baseline (initiation of ETN), and at time of disease flare. After ETN withdrawal, 66 of the 110 patients enrolled (60%) flared with arthritis (of whom 7 flared with concurrent anterior uveitis; none with uveitis alone). The median time to flare was 4.3 months (interquartile range 2.5-6.4) with no evident differences between oJIA and pJIA. The number and type of joints involved at baseline and characteristics of ETN treatment/discontinuation were not associated with flare. Patients who flared were more frequently males (p = 0.034), positive for antinuclear antibody (ANA; p = 0.047), and had higher values of C-reactive protein (CRP; p = 0.012) at baseline. These variables remained significantly associated with flare in a multivariate logistic analysis, a model accounting for only 14% of the variability of the occurrence of the flare. Our results show that a significant proportion of patients with JIA who maintain CID for at least 6 months experience a relapse after ETN withdrawal. Male sex, presence of ANA, and elevated CRP at baseline were associated with higher risk of flare.

Comparable Efficacy of Abatacept Used as First-line or Second-line Biological Agent for Severe Juvenile Idiopathic Arthritis-related Uveitis.

PubMed

Birolo, Carolina; Zannin, Maria Elisabetta; Arsenyeva, Svetlana; Cimaz, Rolando; Miserocchi, Elisabetta; Dubko, Margarita; Deslandre, Chantal Job; Falcini, Fernanda; Alessio, Maria; La Torre, Francesco; Denisova, Ekaterina; Martini, Giorgia; Nikishina, Irina; Zulian, Francesco

2016-11-01

Abatacept (ABA) has recently been proposed as second-line treatment in patients with juvenile idiopathic arthritis (JIA)-associated uveitis refractory to anti-tumor necrosis factor-α (anti-TNF) agents, but little is known about its efficacy as a first-line approach. The aim of the present study was to compare the safety and efficacy of ABA as a first-line biological agent (ABA-1) with that of ABA as a second-line treatment after 1 or more anti-TNF agents (ABA-2), in patients with severe JIA-related uveitis. In this multicenter study, we collected data on patients with severe JIA-related uveitis treated with ABA as a first-line or second-line biological agent. Changes in frequency of uveitis flares/year and ocular complications before and after ABA treatment, clinical remission, and side effects were recorded. Thirty-five patients with a mean age of 10.8 years were treated with ABA for a mean period of 19.6 months. In 4 patients, ABA administration was discontinued, owing to inefficacy on arthritis in 3 cases and allergic reaction in 1. Thirty-one patients, 14 in the ABA-1 group and 17 in the ABA-2 group, completed the 12-month followup period; of these, 17 (54.8%) had clinical remission. The mean frequency of uveitis flares decreased from 4.1 to 1.2 in the ABA-1 group (p = 0.002) and from 3.7 to 1.2 in the ABA-2 group (p = 0.004). Preexisting ocular complications improved or remained stable in all but 5 patients, all in the ABA-2 group. No significant difference was found between the efficacy of the 2 treatment modalities. ABA confirmed its good safety profile. ABA, used as first-line biological treatment or after 1 or more anti-TNF agents, induces a comparable improvement in severe refractory JIA-related uveitis.

Fine-mapping the MHC locus in juvenile idiopathic arthritis (JIA) reveals genetic heterogeneity corresponding to distinct adult inflammatory arthritic diseases.

PubMed

Hinks, A; Bowes, J; Cobb, J; Ainsworth, H C; Marion, M C; Comeau, M E; Sudman, M; Han, B; Becker, M L; Bohnsack, J F; de Bakker, P I W; Haas, J P; Hazen, M; Lovell, D J; Nigrovic, P A; Nordal, E; Punnaro, M; Rosenberg, A M; Rygg, M; Smith, S L; Wise, C A; Videm, V; Wedderburn, L R; Yarwood, A; Yeung, R S M; Prahalad, S; Langefeld, C D; Raychaudhuri, S; Thompson, S D; Thomson, W

2017-04-01

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases, comprising seven categories. Genetic data could potentially be used to help redefine JIA categories and improve the current classification system. The human leucocyte antigen (HLA) region is strongly associated with JIA. Fine-mapping of the region was performed to look for similarities and differences in HLA associations between the JIA categories and define correspondences with adult inflammatory arthritides. Dense genotype data from the HLA region, from the Immunochip array for 5043 JIA cases and 14 390 controls, were used to impute single-nucleotide polymorphisms, HLA classical alleles and amino acids. Bivariate analysis was performed to investigate genetic correlation between the JIA categories. Conditional analysis was used to identify additional effects within the region. Comparison of the findings with those in adult inflammatory arthritic diseases was performed. We identified category-specific associations and have demonstrated for the first time that rheumatoid factor (RF)-negative polyarticular JIA and oligoarticular JIA are genetically similar in their HLA associations. We also observe that each JIA category potentially has an adult counterpart. The RF-positive polyarthritis association at HLA-DRB1 amino acid at position 13 mirrors the association in adult seropositive rheumatoid arthritis (RA). Interestingly, the combined oligoarthritis and RF-negative polyarthritis dataset shares the same association with adult seronegative RA. The findings suggest the value of using genetic data in helping to classify the categories of this heterogeneous disease. Mapping JIA categories to adult counterparts could enable shared knowledge of disease pathogenesis and aetiology and facilitate transition from paediatric to adult services. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Cross-cultural adaptation and psychometric evaluation of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR) in 54 languages across 52 countries: review of the general methodology.

PubMed

Bovis, Francesca; Consolaro, Alessandro; Pistorio, Angela; Garrone, Marco; Scala, Silvia; Patrone, Elisa; Rinaldi, Mariangela; Villa, Luca; Martini, Alberto; Ravelli, Angelo; Ruperto, Nicolino

2018-04-01

The aim of this project was to cross-culturally adapt and validate the Juvenile Arthritis Multidimensional Assessment Report (JAMAR) questionnaire in 54 languages across 52 different countries that are members of the Paediatric Rheumatology International Trials Organisation (PRINTO). This effort was part of a wider project named Epidemiology and Outcome of Children with Arthritis (EPOCA) to obtain information on the frequency of juvenile idiopathic arthritis (JIA) categories in different geographic areas, the therapeutic approaches adopted, and the disease status of children with JIA currently followed worldwide. A total of 13,843 subjects were enrolled from the 49 countries that took part both in the cross-cultural adaptation phase and in the related validation and data collection: Algeria, Argentina, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Croatia, Czech Republic, Denmark, Ecuador, Egypt, Estonia, Finland, France, Georgia, Germany, Greece, Hungary, India, Islamic Republic of Iran, Israel, Italy, Latvia, Libya, Lithuania, Mexico, Netherlands, Norway, Oman, Paraguay, Poland, Portugal, Romania, Russian Federation, Saudi Arabia, Serbia, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Thailand, Turkey, Ukraine, United Kingdom and United States of America. 9021 patients had JIA (10.7% systemic arthritis, 41.9% oligoarthritis, 23.5% RF negative polyarthritis, 4.2% RF positive polyarthritis, 3.4% psoriatic arthritis, 10.6% enthesitis-related arthritis and 5.7% undifferentiated arthritis) while 4822 were healthy children. This introductory paper describes the overall methodology; results pertaining to each country are fully described in the accompanying manuscripts. In conclusion, the JAMAR translations were found to have satisfactory psychometric properties and it is thus a reliable and valid tool for the multidimensional assessment of children with JIA.

Long‐Term Safety, Efficacy, and Quality of Life in Patients With Juvenile Idiopathic Arthritis Treated With Intravenous Abatacept for Up to Seven Years

PubMed Central

Ruperto, Nicolino; Mouy, Richard; Paz, Eliana; Rubio‐Pérez, Nadina; Silva, Clovis A.; Abud‐Mendoza, Carlos; Burgos‐Vargas, Ruben; Gerloni, Valeria; Melo‐Gomes, Jose A.; Saad‐Magalhaes, Claudia; Chavez‐Corrales, J.; Huemer, Christian; Kivitz, Alan; Blanco, Francisco J.; Foeldvari, Ivan; Hofer, Michael; Huppertz, Hans‐Iko; Job Deslandre, Chantal; Minden, Kirsten; Punaro, Marilynn; Block, Alan J.; Giannini, Edward H.; Martini, Alberto

2015-01-01

Objective The efficacy and safety of abatacept in patients with juvenile idiopathic arthritis (JIA) who experienced an inadequate response to disease‐modifying antirheumatic drugs were previously established in a phase III study that included a 4‐month open‐label lead‐in period, a 6‐month double‐blind withdrawal period, and a long‐term extension (LTE) phase. The aim of this study was to present the safety, efficacy, and patient‐reported outcomes of abatacept treatment (10 mg/kg every 4 weeks) during the LTE phase, for up to 7 years of followup. Methods Patients enrolled in the phase III trial could enter the open‐label LTE phase if they had not achieved a response to treatment at month 4 or if they had received abatacept or placebo during the double‐blind period. Results One hundred fifty‐three (80.5%) of 190 patients entered the LTE phase, and 69 patients (36.3%) completed it. The overall incidence rate (events per 100 patient‐years) of adverse events decreased during the LTE phase (433.61 events during the short‐term phase [combined lead‐in and double‐blind periods] versus 132.39 events during the LTE phase). Similar results were observed for serious adverse events (6.82 versus 5.60), serious infections (1.13 versus 1.72), malignancies (1.12 versus 0), and autoimmune events (2.26 versus 1.18). American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) responses, Pedi 70 responses, and clinically inactive disease status were maintained throughout the LTE phase in patients who continued to receive therapy. Improvements in the Child Health Questionnaire physical and psychosocial summary scores were maintained over time. Conclusion Long‐term abatacept treatment for up to 7 years was associated with consistent safety, sustained efficacy, and quality‐of‐life benefits in patients with JIA. PMID:26097215

Macrophage activation syndrome in children with systemic juvenile idiopathic arthritis and systemic lupus erythematosus.

PubMed

Aytaç, Selin; Batu, Ezgi Deniz; Ünal, Şule; Bilginer, Yelda; Çetin, Mualla; Tuncer, Murat; Gümrük, Fatma; Özen, Seza

2016-10-01

Macrophage activation syndrome (MAS) is a hyper-inflammatory disorder secondary to a rheumatic disease such as systemic juvenile idiopathic arthritis (SJIA) and systemic lupus erythematosus (SLE). We aimed to present the characteristics of our pediatric MAS patients. Clinical features, laboratory parameters, treatment, and outcome of 34 patients (28 SJIA; six SLE; 37 MAS episodes) followed at a tertiary health center between 2009 and 2015 were retrospectively reviewed. The median age at MAS onset was 11 years. More SJIA patients had MAS at disease onset than SLE patients (53.6 vs. 16.7 %). Fever, high C-reactive protein and hyperferritinemia were present in all MAS episodes. Rash was less (p = 0.03), and fatigue was more frequent (p = 0.042) in SLE than SJIA patients. All received corticosteroids. Cyclosporine was given in 74.2 % of SJIA-MAS; 66.7 % of SLE-MAS episodes. Intravenous immunoglobulin, anakinra, or etoposide was administered during 67.7; 41.9; 32.3 % of SJIA-MAS and 33.3; 33.3; 50 % of SLE-MAS episodes, respectively. Plasmapheresis was performed during 41.9 % of SJIA-MAS and 33.3 % of SLE-MAS episodes. The mortality rate was 11.8 % (n = 4;3 SJIA, 1 SLE). Hepatosplenomegaly was more frequent (p = 0.005), and plasmapheresis was performed more frequently (p = 0.021) in the patients who died compared to the cured patients. The median duration between symptom onset and admission to our hospital was longer among the patients who died (16.5 vs. 7 days; p = 0.049). Our patients' characteristics were similar to the reported cases, but our mortality rate is slightly higher probably due to late referral to our center. Early diagnosis and effective treatment are crucial to prevent mortality.

Quantifying the Effect of Temporomandibular Joint Intra-Articular Steroid Injection on Synovial Enhancement in Juvenile Idiopathic Arthritis.

PubMed

Resnick, Cory M; Vakilian, Pouya M; Kaban, Leonard B; Peacock, Zachary S

2016-12-01

To quantify the effect of intra-articular steroid injections (IASIs) on temporomandibular joint (TMJ) synovitis in children with juvenile idiopathic arthritis (JIA) using gadolinium-enhanced magnetic resonance imaging (MRI). The present study was a retrospective study of children with JIA who had undergone TMJ IASIs at Boston Children's Hospital. The patients were included if they had undergone contrast-enhanced MRI both before and after IASI and if the pre-IASI MRI had demonstrated synovitis (enhancement ratio [ER] >1.55). Patients with TMJ pathology or pain unrelated to JIA or a history of facial trauma were excluded. The predictor variables were age, gender, JIA subtype, exposure to medications for arthritis, and a family history of autoimmune disease. The primary outcome variable was the ER. Additional outcome variables included patient-reported pain and the maximal incisal opening (MIO). Twenty-nine subjects (83% female) with a total of 50 injected TMJs were included. The average age at JIA diagnosis and at IASI was 6.8 ± 1.7 years and 12.1 ± 1.9 years, respectively. The mean follow-up period was 22.9 ± 4.3 months (range 5 to 48). The ER decreased in all injected joints, with a mean reduction of 1.05 ± 1.01 (P < .001). The post-IASI ER was less than the normal threshold (1.55) in 18% of the injected TMJs. IASI was associated with an elimination of pain in 89% of the subjects (P < .001) and in augmentation of the MIO by 5.8 ± 2.6 mm (P < .001). In children with JIA and TMJ synovitis, TMJ IASI was associated with a reduction in synovial enhancement, decreased pain, and an increased MIO. Only 18% of injected joints, however, experienced complete resolution of synovitis. These results support the use of IASI in the management of the pain and dysfunction associated with TMJ synovitis. Further study is required to determine the efficacy of IASI in limiting inflammation and future joint destruction. Copyright © 2016 American Association of Oral and

Reversible posterior leukoencephalopathy syndrome secondary to systemic-onset juvenile idiopathic arthritis: A case report and review of the literature.

PubMed

Zhang, Pingping; Li, Xiaofeng; Li, Yating; Wang, Jing; Zeng, Huasong; Zeng, Xiaofeng

2015-01-01

Reversible posterior leukoencephalopathy syndrome (RPLS) is a clinical syndrome based on changes in clinical imaging, and it has been reported to mainly occur in adults. However, it has been recently discovered that RPLS is also prevalent in infant patients, particularly in those using glucocorticoids, immunosuppressant medications and cytotoxic drugs. The current study presents a 5-year-old male with a previous diagnosis of systemic-onset juvenile idiopathic arthritis (SoJIA) and macrophage-activation syndrome who developed posterior reversible encephalopathy syndrome during treatment with glucocorticoids, disease-modifying antirheumatic drugs and biological agent (etanercept) therapy. After ~5 days of treatment, the patient made a complete clinical recovery; the magnetic resonance imaging reviewed 2 weeks later showed that the previous hyper-intensity signal had disappeared and the multiple lesions in the brain had been completely absorbed. The case report shows that, conforming to recent literature, SoJIA in infants should be considered a risk factor for developing RPLS. The clinical manifestations of the disease are multiple, but usually reversible, and the patients mostly have a good prognosis. Rapid diagnosis and treatment is essential as early treatment may prevent progression to irreversible brain damage. By increasing the awareness of RPLS, the patient care may improve and further insight may be gained.

Familial aggregation of arthritis-related diseases in seropositive and seronegative rheumatoid arthritis: a register-based case-control study in Sweden

PubMed Central

Frisell, Thomas; Hellgren, Karin; Alfredsson, Lars; Raychaudhuri, Soumya; Klareskog, Lars; Askling, Johan

2015-01-01

Objectives Our objective was to estimate the risk of developing rheumatoid arthritis (RA) associated with a family history of non-RA arthritis-related diseases. This familial co-aggregation is of clinical interest since it is often encountered when assessing family history of RA specifically, but also informative on the genetic overlap between these diseases. Since anticitrullinated peptide antibodies/rheumatoid factor (RF)-positive and RF-negative RA have both specific and shared genetic factors, the familial co-aggregation was assessed separately for seropositive and seronegative disease. Methods Nested case-control study in prospectively recorded Swedish total population data. The Multi-Generation Register identified first-degree relatives. RA and arthritis-related diseases were ascertained through the nationwide patient register. RA serology was based on International Classification of Diseases tenth revision coded diagnoses, mainly reflecting RF. Familial risks were calculated using conditional logistic regression. Results were replicated using the Swedish rheumatology register. Results Familial co-aggregation was found between RA and every studied arthritis-related disease, but the magnitude varied widely, from juvenile idiopathic arthritis (JIA) (seropositive RA OR=3.98 (3.01 to 5.26); seronegative RA OR=5.70 (3.47 to 9.36)) to osteoarthritis (seropositive RA OR=1.03 (1.00 to 1.06); seronegative RA OR=1.05 (1.00 to 1.09)). The familial co-aggregation pattern of non-RA arthritis-related diseases was overall similar for seropositive and seronegative RA. Among those with family history of RA, relatives’ other arthritis-related diseases conferred little or no additional risk. Conclusions Although family history of several arthritis-related diseases may be useful to predict RA (eg, lupus and JIA), others (eg, osteoarthritis and arthralgia) are less useful. Seropositive and seronegative RA had rather similar familial co-aggregation patterns with arthritis

Familial aggregation of arthritis-related diseases in seropositive and seronegative rheumatoid arthritis: a register-based case-control study in Sweden.

PubMed

Frisell, Thomas; Hellgren, Karin; Alfredsson, Lars; Raychaudhuri, Soumya; Klareskog, Lars; Askling, Johan

2016-01-01

Our objective was to estimate the risk of developing rheumatoid arthritis (RA) associated with a family history of non-RA arthritis-related diseases. This familial co-aggregation is of clinical interest since it is often encountered when assessing family history of RA specifically, but also informative on the genetic overlap between these diseases. Since anticitrullinated peptide antibodies/rheumatoid factor (RF)-positive and RF-negative RA have both specific and shared genetic factors, the familial co-aggregation was assessed separately for seropositive and seronegative disease. Nested case-control study in prospectively recorded Swedish total population data. The Multi-Generation Register identified first-degree relatives. RA and arthritis-related diseases were ascertained through the nationwide patient register. RA serology was based on International Classification of Diseases tenth revision coded diagnoses, mainly reflecting RF. Familial risks were calculated using conditional logistic regression. Results were replicated using the Swedish rheumatology register. Familial co-aggregation was found between RA and every studied arthritis-related disease, but the magnitude varied widely, from juvenile idiopathic arthritis (JIA) (seropositive RA OR=3.98 (3.01 to 5.26); seronegative RA OR=5.70 (3.47 to 9.36)) to osteoarthritis (seropositive RA OR=1.03 (1.00 to 1.06); seronegative RA OR=1.05 (1.00 to 1.09)). The familial co-aggregation pattern of non-RA arthritis-related diseases was overall similar for seropositive and seronegative RA. Among those with family history of RA, relatives' other arthritis-related diseases conferred little or no additional risk. Although family history of several arthritis-related diseases may be useful to predict RA (eg, lupus and JIA), others (eg, osteoarthritis and arthralgia) are less useful. Seropositive and seronegative RA had rather similar familial co-aggregation patterns with arthritis-related diseases, suggesting that the two RA

Cost-Effectiveness of TNF-Blocker Injection Spacing for Patients with Established Rheumatoid Arthritis in Remission: An Economic Evaluation from the Spacing of TNF-Blocker Injections in Rheumatoid Arthritis Trial.

PubMed

Vanier, Antoine; Mariette, Xavier; Tubach, Florence; Fautrel, Bruno

2017-04-01

In patients with rheumatoid arthritis in remission, a disease activity-driven tapering of adalimumab or etanercept relying on progressive injection spacing has not been shown to be equivalent to a maintenance strategy at full dose in terms of disease activity in the Spacing of TNF-blocker injections in Rheumatoid ArthritiS Study (STRASS) trial. To evaluate the cost-effectiveness of such a spacing strategy based on the data of the STRASS trial. This is a cost-utility analysis of the STRASS trial, a French multicenter 18-month equivalence randomized open-label controlled trial that included patients at stable dose for at least 1 year, in remission for at least 6 months. Effectiveness was assessed in quality-adjusted life-years (QALYs). Costs involved in the study period were assessed from a payer perspective. The decremental cost-effectiveness ratio (DCER) was calculated in the complete cases sample (n = 98). Several sensitivity analyses were conducted and the impact of missing data on DCER estimate was investigated. An acceptability analysis was performed. In the spacing arm, TNF-blockers were stopped for 34.1% of the patients, tapered for 43.2%, and maintained at full dose for 18.2%. The spacing strategy was associated with less QALYs gain (mean difference of -0.158; 95% confidence interval [CI] -0.085 to -0.232) and reduced costs (mean difference of -€8,440; 95% CI -6,507 to -10,212). The estimated DCER of the spacing strategy over the maintenance at full dose was €53,417 saved per QALY lost (95% CI 32,230 to 104,700). The spacing strategy appears cost-effective, but the acceptability of such a QALY loss reported to the cost avoided remains to be evaluated, because no consensual threshold has been determined for willingness to accept as compared with willingness to pay. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Orthodontic and dentofacial orthopedic management of juvenile idiopathic arthritis: a systematic review of the literature.

PubMed

von Bremen, J; Ruf, S

2011-08-01

To systematically review the literature published on orthodontic treatment principles in patients with juvenile idiopathic arthritis (JIA). Several electronic databases (PubMed, Medpilot, Web of Science, and DIMDI) and orthodontic and rheumatologic literature were systematically searched for studies published until May 2010. The articles were rated by two independent reviewers and included after three selection steps (title-abstract-full text). Articles had to be studies performed on ≥ 5 patients with a disease onset before the age of 16. The selection process resulted in the inclusion of three publications on dentofacial orthopedics and six on combined surgical orthodontic therapy. The three studies on dentofacial orthopedics aimed to improve the mandibular retrusion by means of removable functional appliances (activator). Whereas these orthodontic approaches comprised relatively large and homogeneous patient samples (14, 22, and 72 subjects, aged 6-16), the surgical studies were basically case series with a large age span of the patients (5-12 subjects, aged 10-44). In these surgical treatment approaches, orthodontics was limited to pre-surgical leveling and post-surgical finishing, while the skeletal discrepancy was treated surgically by a variety of techniques (costochondral grafts, bilateral sagittal spilt osteotomy, Le Fort I, and genioplasty). The treatment goals of both approaches were improvement of esthetics and function and/or pain reduction, and both approaches showed satisfactory results. Because of the heterogeneity of the subject material and the low level of evidence of the papers, it is difficult to draw any conclusions on the orthodontic/dentofacial orthopedic management of JIA. It appears as if removable functional appliances may be beneficial in adolescent patients with JIA. © 2011 John Wiley & Sons A/S.

Fundamental movement skills, physical fitness and physical activity among Australian children with juvenile idiopathic arthritis.

PubMed

Hulsegge, Gerben; Henschke, Nicholas; McKay, Damien; Chaitow, Jeffrey; West, Kerry; Broderick, Carolyn; Singh-Grewal, Davinder

2015-04-01

To describe fundamental movement skills (FMS), physical fitness and level of physical activity among Australian children with juvenile idiopathic arthritis (JIA) and compare this with healthy peers. Children aged 6-16 years with JIA were recruited from hospital rheumatology clinics and private rheumatology rooms in Sydney, Australia. All children attended an assessment day, where FMS were assessed by a senior paediatric physiotherapist, physical fitness was assessed using the multistage 20-metre shuttle run test, and physical activity and physical and psychosocial well-being were assessed with questionnaires. These results were compared with age- and gender-matched peers from the NSW Schools Physical Activity and Nutrition Survey and the Health of Young Victorians Study using logistic regression analysis. Twenty-eight children with JIA participated in this study. There were no differences in the proportion of children who had mastered FMS between children with JIA and their healthy peers (P > 0.05). However, there was a trend for children with JIA to have poorer physical fitness and be less physically active than healthy peers. Parents of children with JIA indicated more physical and psychosocial impairments among their children and themselves compared with parents of healthy children (P < 0.05). This is the first study in Australia to compare FMS, physical activity and fitness in children with JIA and their peers. While older children with JIA appear to have poorer physical fitness and physical activity levels than their peers, there is no difference in FMS. © 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Patient-reported outcomes as end points in clinical trials in rheumatoid arthritis

PubMed Central

Gossec, Laure; Dougados, Maxime; Dixon, William

2015-01-01

There is a growing interest in patient-reported outcomes (PROs) in rheumatology, which goes with a global trend for more ‘patient-centred care’. This review considers the use of PROs in trials, including their strengths and limitations. In rheumatoid arthritis (RA) trials, the most frequently used PROs to assess treatments include pain, patient global assessment, assessment of functional status, but also health-related quality of life and less commonly fatigue. Other aspects of importance for patients, such as sleep, psychological well-being or ability to cope, are rarely assessed. PROs as outcome measures in RA trials have strengths as well as limitations. PROs have face validity, they are reproducible and sensitive to change and they bring additional information beyond joint counts or acute phase reactants. However, their predictive validity for later outcomes has been little explored, some PROs show redundancy (they bring similar information) and, due to the apparently moderate link between some PROs such as fatigue and the disease process, the use of some PROs to inform treatment choices has been questioned. We suggest the choice of PROs for trials depends on the study objective and on the viewpoint of the stakeholder. There needs to be agreed prioritisation across all stakeholders about what is most important to collect in a trial, which is why a prioritisation and selection process is necessary. Trials in RA will continue to include PROs and their interpretation will become easier as our knowledge progresses. PMID:26509052

Perspective: Update on Idiopathic Intracranial Hypertension

PubMed Central

Bruce, Beau B.; Biousse, Valérie; Newman, Nancy J.

2011-01-01

Purpose Provide an update on various features of idiopathic intracranial hypertension. Design Perspective. Methods Selected articles on the epidemiology, clinical and imaging features, natural history, pathophysiology, and treatment of idiopathic intracranial hypertension were reviewed and interpreted in the context of the authors’ clinical and research experience. Results Idiopathic intracranial hypertension is primarily a disease of obese women of childbearing age, but it can affect patients of any weight, sex, and age. Although a relatively rare disorder, idiopathic intracranial hypertension’s associated costs in the U.S. entail hundreds of millions of dollars. Even following treatment, headaches are frequently persistent and may require the continued involvement of a neurologist. Quality of life reductions and depression are common among idiopathic intracranial hypertension patients. However, visual dysfunction, especially visual field abnormalities, represents the major morbidity of this disorder, and serial automated perimetry remains the primary mode of patient monitoring. Patients who are men, black, very obese, or anemic are at higher risk of visual loss. Vitamin A metabolism, adipose tissue as an actively secreting endocrine tissue, and cerebral venous abnormalities are areas of active study regarding idiopathic intracranial hypertension’s pathophysiology. Treatment studies show that lumbar puncture is a valuable treatment (in addition to its crucial diagnostic role) and that weight management is critical. However, open questions remain regarding the efficacy of acetazolamide, CSF diversion procedures, and cerebral venous stenting. Conclusions Many questions remain unanswered about idiopathic intracranial hypertension. Ongoing studies, especially an ongoing NIH-funded clinical trial of acetazolamide, should provide more insight into this important, yet poorly understood syndrome of isolated intracranial hypertension. PMID:21696699

[Determination of 25(OH)D serum levels in children with systemic lupus erythematosus and juvenile idiopathic arthritis].

PubMed

Rosiles, Vanessa Hernández; Salazar, Carolina Duarte; Velazquez, Rocío Maldonado; Ruiz, Rodolfo Rivas; Clark, Patricia

It is well recognized that vitamin D has a direct effect in bone and muscle and has been associated as well with some rheumatologic diseases. Reports in children are scarce. The aim of this study was to determine the concentration level of 25(OH)D in a group of patients with systemic lupus erythematosus (SLE) and juvenile idiopathic arthritis (JIA) and compare them with healthy controls. Vitamin D (25(OH)D) was measured with isotope-dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS), PTH with immunoradiometric assay (IRMA), calcium, phosphorus and alkaline phosphatase by colorimetric assay in 37 patients with SLE, 37 patients with JIA and 79 healthy controls. Mean 25(OH)D concentration levels were as follows: SLE 18.9±7.92ng/ml, JIA 21.97±5.55ng/ml and 23.6±3.07ng/ml in healthy controls. There was a significant difference between SLE patients vs. healthy controls (p <0.05); 29.7% of SLE patients, 35.1% of JIA patients and 31.6% of healthy controls had deficient levels of vitamin D. One third of the total sample of children in this study had deficient levels of vitamin D. Patients with SLE presented a significant difference compared with healthy controls. Copyright © 2015 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Definition of improvement in juvenile idiopathic arthritis using the juvenile arthritis disease activity score.

PubMed

Horneff, Gerd; Becker, Ingrid

2014-07-01

The aim of this study was to define improvement thresholds for the Juvenile Arthritis Disease Activity Score (JADAS). Physicians' and parents' judgements on treatment efficacy, the ACR paediatric response measure (PedACR) and JADAS were extracted from BIKER. Patients were categorized by baseline classes in the 10-joint JADAS (JADAS10) as low (5 to <15), moderate (15 to <25) and high (25 to ≤40). Cut-offs for defining improvement following treatment with biologics or MTX were chosen by calculating the interquartile ranges (IQRs) of the judgement groups and considering the accuracy, sensitivity and specificity of the resulting model. Differences in the change of JADAS10 by JIA category were also analysed by analysis of variance (ANOVA). Sensitivity, specificity and accuracy were calculated. A total of 1315 treatment courses were analysed. The ANOVA of the JIA categories showed no significant differences of the mean JADAS10 in all baseline classes and IQRs also showed good overall limits. Therefore all JIA categories were combined for a collective cut-off. Analysis by baseline class revealed clear cut-off points. Improvement could be defined by the minimal decrease in the JADAS10 in baseline class low by 4 (41%), moderate by 10 (53%) and high by 17 (57%). The model shows values for accuracy from 75.6 to 85.5% and comparable values for sensitivity and specificity. Improvement after 3 months can be defined efficiently by the decrease of the JADAS10, depending on the baseline JADAS10 score, which specifies low, moderate or high disease activity. Our model demonstrates clear cut-off values. The JADAS10 may be used in addition to ACR criteria in clinical trials. Also, since the JADAS10 can easily be calculated at each patient visit, it also can be used for clinical decisions. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Prevalence of juvenile idiopathic arthritis in children aged 6 to 12 years in Embu das Artes, state of Sao Paulo, Brazil.

PubMed

Yamashita, Edson; Terreri, Maria Teresa R A; Hilário, Maria Odete E; Len, Claudio A

2013-01-01

The aim of the study was to study the prevalence of juvenile idiopathic arthritis (JIA) in school children in the city of Embu das Artes in São Paulo State. 2880 school children from seven public schools, aged between 6 and 12 years, were evaluated (clinical findings) by a pediatric rheumatologist. A board certified Pediatric Rheumatologist evaluated the subjects with suspected inflammatory arthropathy. Children with higher suspicion were referred to a specialized service. One hundred and forty-one children have presented abnormalities on examination of musculoskeletal system, with isolated pain on palpation the most common finding in the first evaluation (60.9%), with improvement in almost all cases in the second examination. Most of the abnormalities were related to recent injuries or congenital malformations. Six children have clinical findings suggestive of chronic arthropathy and were referred to a specialized pediatric rheumatology clinic. Of these, a 12 year-old girl fulfilled the criteria for JIA. The other diagnoses were aseptic necrosis of the hip (P = 1) of and post-trauma synovitis (P = 4). The prevalence of JIA in children aged between 6 and 12 years was 1/2.880 (or 0.34/1.000).

Genome-Wide Association Meta-Analysis Reveals Novel Juvenile Idiopathic Arthritis Susceptibility Loci.

PubMed

McIntosh, Laura A; Marion, Miranda C; Sudman, Marc; Comeau, Mary E; Becker, Mara L; Bohnsack, John F; Fingerlin, Tasha E; Griffin, Thomas A; Haas, J Peter; Lovell, Daniel J; Maier, Lisa A; Nigrovic, Peter A; Prahalad, Sampath; Punaro, Marilynn; Rosé, Carlos D; Wallace, Carol A; Wise, Carol A; Moncrieffe, Halima; Howard, Timothy D; Langefeld, Carl D; Thompson, Susan D

2017-11-01

Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease and has a strong genomic component. To date, JIA genetic association studies have had limited sample sizes, used heterogeneous patient populations, or included only candidate regions. The aim of this study was to identify new associations between JIA patients with oligoarticular disease and those with IgM rheumatoid factor (RF)-negative polyarticular disease, which are clinically similar and the most prevalent JIA disease subtypes. Three cohorts comprising 2,751 patients with oligoarticular or RF-negative polyarticular JIA were genotyped using the Affymetrix Genome-Wide SNP Array 6.0 or the Illumina HumanCoreExome-12+ Array. Overall, 15,886 local and out-of-study controls, typed on these platforms or the Illumina HumanOmni2.5, were used for association analyses. High-quality single-nucleotide polymorphisms (SNPs) were used for imputation to 1000 Genomes prior to SNP association analysis. Meta-analysis showed evidence of association (P < 1 × 10 -6 ) at 9 regions: PRR9_LOR (P = 5.12 × 10 -8 ), ILDR1_CD86 (P = 6.73 × 10 -8 ), WDFY4 (P = 1.79 × 10 -7 ), PTH1R (P = 1.87 × 10 -7 ), RNF215 (P = 3.09 × 10 -7 ), AHI1_LINC00271 (P = 3.48 × 10 -7 ), JAK1 (P = 4.18 × 10 -7 ), LINC00951 (P = 5.80 × 10 -7 ), and HBP1 (P = 7.29 × 10 -7 ). Of these, PRR9_LOR, ILDR1_CD86, RNF215, LINC00951, and HBP1 were shown, for the first time, to be autoimmune disease susceptibility loci. Furthermore, associated SNPs included cis expression quantitative trait loci for WDFY4, CCDC12, MTP18, SF3A1, AHI1, COG5, HBP1, and GPR22. This study provides evidence of both unique JIA risk loci and risk loci overlapping between JIA and other autoimmune diseases. These newly associated SNPs are shown to influence gene expression, and their bounding regions tie into molecular pathways of immunologic relevance. Thus, they likely represent regions that contribute to the pathology of oligoarticular JIA and RF

Juvenile idiopathic arthritis activity and function ability: deleterious effects in periodontal disease?

PubMed

Pugliese, Camila; van der Vinne, Roberta T A; Campos, Lucia M A; Guardieiro, Priscila R; Saviolli, Cynthia; Bonfá, Eloisa; Pereira, Rosa M R; Viana, Vilma S; Borba, Eduardo F; Silva, Clovis A

2016-01-01

The impact of juvenile idiopathic arthritis (JIA) in periodontal diseases is controversial probably due to gender and age heterogeneity. We therefore evaluated a homogeneous female post-pubertal JIA population for these conditions. Thirty-five JIA patients and 35 gender/age comparable healthy controls were evaluated according to demographic data, complete periodontal evaluation, fasting lipoproteins, and anti-lipoprotein lipase antibodies. JIA scores, laboratorial tests, X-rays, and treatment were also assessed. Current age was similar in JIA patients and controls (11.90 ± 2.0 vs. 12.50 ± 3.0 years, p = 0.289). Complete periodontal assessments revealed that gingival index, dental plaque, gingival bleeding, and clinical dental attachment indices were alike in JIA patients and controls (p > 0.05), except for gingival enlargement in former group (p < 0.0001). Further analysis of patients with and without gingivitis revealed that cyclosporine use was more often observed in JIA patients with gingivitis (37 vs. 0%, p = 0.01), whereas no differences were evidenced in demographic, JIA scores, inflammatory markers, and lipid profile in both groups. Of note, two parameters of periodontal assessment were correlated with JIA scores [gingival index (GI) and Childhood Health Assessment Questionnaire (CHAQ) (r s  = +0.402, p = 0.020)] and plaque index (PI) and visual analog scale (VAS) physician (r s  = +0.430, p = 0.013). In addition, evaluation of dental assessment demonstrated that JIA activity scores had positive correlation with decayed, missing, and filled teeth (DMF-T) and junvenile athritis disease activity score (JADAS) (r s  = +0.364,p = 0.037), VAS physician (r s  = +0.401,p = 0.021) and VAS patient (r s  = +0.364,p = 0.037). We demonstrated, using rigorous criteria, that periodontal and dental condition in JIA is similar to controls. In spite of that, the finding of a correlation with disease parameters

Herbal medicine for idiopathic central precocious puberty: A protocol for a systematic review of controlled trials.

PubMed

Lee, Hye Lim; Lee, Yoo Been; Choi, Jun-Yong; Lee, Ju Ah

2018-03-01

Herbal medicine is widely used in East Asia to treat idiopathic central precocious puberty (ICPP). Most of the available clinical trials that investigated herbal medicine for ICPP have been included in this review. This systematic review will assess the efficacy and safety of herbal medicine for ICPP. Eleven databases, including Asian databases, will be searched for studies conducted through 2018. We will include randomized controlled trials assessing herbal medicine for ICPP. The risk of bias will be evaluated using the Cochrane risk of bias assessment tool, and confidence in the cumulative evidence will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation instrument. This systematic review will be published in a peer-reviewed journal and disseminated both electronically and in print. The review will be updated to inform and guide health care practices. PROSPER 2018 CRD42018087988.

Guidelines for the medical treatment of idiopathic pulmonary fibrosis.

PubMed

Xaubet, Antoni; Molina-Molina, María; Acosta, Orlando; Bollo, Elena; Castillo, Diego; Fernández-Fabrellas, Estrella; Rodríguez-Portal, José Antonio; Valenzuela, Claudia; Ancochea, Julio

2017-05-01

Idiopathic pulmonary fibrosis is defined as chronic fibrosing interstitial pneumonia limited to the lung, with poor prognosis. The incidence has been rising in recent years probably due to improved diagnostic methods and increased life expectancy. In 2013, the SEPAR guidelines for the diagnosis and treatment for idiopathic pulmonary fibrosis were published. Since then, clinical trials and meta-analyses have shown strong scientific evidence for the use of pirfenidone and nintedanib in the treatment of idiopathic pulmonary fibrosis. In 2015, the international consensus of 2011 was updated and new therapeutic recommendations were established, prompting us to update our recommendation for the medical treatment of idiopathic pulmonary fibrosis accordingly. Diagnostic aspects and non-pharmacological treatment will not be discussed as no relevant developments have emerged since the 2013 guidelines. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Infections in children and adolescents with juvenile idiopathic arthritis and inflammatory bowel disease treated with tumor necrosis factor-α inhibitors: systematic review of the literature.

PubMed

Toussi, Sima S; Pan, Nancy; Walters, Heather M; Walsh, Thomas J

2013-11-01

Tumor necrosis factor alpha (TNF-α) inhibitors are increasingly administered to children and adolescents with juvenile idiopathic arthritis (JIA) and pediatric inflammatory bowel disease (pIBD). Adult studies indicate that TNF-α inhibitors lead to an increased risk of serious infections compared to other disease-modifying antirheumatic drugs. We report herein a systematic literature review detailing the epidemiology and types of infections reported in children with JIA and pIBD treated with TNF-α inhibitors. The most frequently reported infections were mild and characterized as viral in etiology. Severe bacterial and fungal infections also occurred, but were less common and possibly associated with intrinsic risk factors and concurrent immunosuppressive therapy. Few pediatric patients developed Mycobacterium tuberculosis, likely due to effective screening. There were 8 infectious fatalities in children treated with TNF-α inhibitors. Overall, although rare, serious infections occur in immunocompromised children and adolescents with JIA and pIBD receiving TNF-α inhibitors.

Infections in Children and Adolescents With Juvenile Idiopathic Arthritis and Inflammatory Bowel Disease Treated With Tumor Necrosis Factor–α Inhibitors: Systematic Review of the Literature

PubMed Central

Toussi, Sima S.; Pan, Nancy; Walters, Heather M.; Walsh, Thomas J.

2013-01-01

Tumor necrosis factor alpha (TNF-α) inhibitors are increasingly administered to children and adolescents with juvenile idiopathic arthritis (JIA) and pediatric inflammatory bowel disease (pIBD). Adult studies indicate that TNF-α inhibitors lead to an increased risk of serious infections compared to other disease-modifying antirheumatic drugs. We report herein a systematic literature review detailing the epidemiology and types of infections reported in children with JIA and pIBD treated with TNF-α inhibitors. The most frequently reported infections were mild and characterized as viral in etiology. Severe bacterial and fungal infections also occurred, but were less common and possibly associated with intrinsic risk factors and concurrent immunosuppressive therapy. Few pediatric patients developed Mycobacterium tuberculosis, likely due to effective screening. There were 8 infectious fatalities in children treated with TNF-α inhibitors. Overall, although rare, serious infections occur in immunocompromised children and adolescents with JIA and pIBD receiving TNF-α inhibitors. PMID:23899685

Daily Sleep Patterns, Sleep Quality, and Sleep Hygiene Among Parent–Child Dyads of Young Children Newly Diagnosed With Juvenile Idiopathic Arthritis and Typically Developing Children

PubMed Central

Chen, Maida Lynn; Cain, Kevin C.; Ringold, Sarah; Wallace, Carol A.; Ward, Teresa M.

2016-01-01

Objectives Describe daily sleep patterns, sleep quality, and sleep hygiene in 2–5-year-old children newly diagnosed with juvenile idiopathic arthritis (JIA) and their parents in comparison with typically developing (TD) children and parents. Methods Participants (13 JIA, 16 TD parent–child dyads) wore actigraphs for 10 days. Parents completed sleep diaries and sleep hygiene survey. Results Children with JIA had significantly less total sleep time, lower sleep efficiency (SE), and longer naps than TD children. Parents of children with JIA had significantly earlier bedtimes, more wake after sleep onset (WASO) and lower SE than TD parents. Parent–child SE and WASO were interrelated in JIA dyads. Sleep hygiene practices were inconsistent in both groups of children. Conclusions Inadequate amounts of sleep and poor sleep quality were common in parent–child dyads. Early interventions to improve sleep duration and promote sleep hygiene practices may alleviate future sleep problems and improve parent and child well-being. PMID:26994855

A Novel Mobile App and Population Management System to Manage Rheumatoid Arthritis Flares: Protocol for a Randomized Controlled Trial.

PubMed

Wang, Penny; Luo, Dee; Lu, Fengxin; Elias, Josephine S; Landman, Adam B; Michaud, Kaleb D; Lee, Yvonne C

2018-04-11

Rheumatoid arthritis flares have a profound effect on patients, causing pain and disability. However, flares often occur between regularly scheduled health care provider visits and are, therefore, difficult to monitor and manage. We sought to develop a mobile phone app combined with a population management system to help track RA flares between visits. The objective of this study is to implement the mobile app plus the population management system to monitor rheumatoid arthritis disease activity between scheduled health care provider visits over a period of 6 months. This is a randomized controlled trial that lasts for 6 months for each participant. We aim to recruit 190 patients, randomized 50:50 to the intervention group versus the control group. The intervention group will be assigned the mobile app and be prompted to answer daily questionnaires sent to their mobile devices. Both groups will be assigned a population manager, who will communicate with the participants via telephone at 6 weeks and 18 weeks. The population manager will also communicate with the participants in the intervention group if their responses indicate a sustained increase in rheumatoid arthritis disease activity. To assess patient satisfaction, the primary outcomes will be scores on the Treatment Satisfaction Questionnaire for Medication as well as the Perceived Efficacy in Patient-Physician Interactions questionnaire at 6 months. To determine the effect of the mobile app on rheumatoid arthritis disease activity, the primary outcome will be the Clinical Disease Activity Index at 6 months. The trial started in November 2016, and an estimated 2.5 years will be necessary to complete the study. Study results are expected to be published by the end of 2019. The completion of this study will provide important data regarding the following: (1) the assessment of validated outcome measures to assess rheumatoid arthritis disease activity with a mobile app between routinely scheduled health care

5-Aminoimidazole-4-carboxamide ribonucleotide-transformylase and inosine-triphosphate-pyrophosphatase genes variants predict remission rate during methotrexate therapy in patients with juvenile idiopathic arthritis.

PubMed

Pastore, Serena; Stocco, Gabriele; Moressa, Valentina; Zandonà, Luigi; Favretto, Diego; Malusà, Noelia; Decorti, Giuliana; Lepore, Loredana; Ventura, Alessandro

2015-04-01

For children with juvenile idiopathic arthritis (JIA) who fail to respond to methotrexate, the delay in identifying the optimal treatment at an early stage of disease can lead to long-term joint damage. Recent studies indicate that relevant variants to predict methotrexate response in JIA are those in 5-aminoimidazole-4-carboxamide ribonucleotide-transformylase (ATIC), inosine-triphosphate-pyrophosphatase (ITPA) and solute-liquid-carrier-19A1 genes. The purpose of the study was, therefore, to explore the role of these candidate genetic factors on methotrexate response in an Italian cohort of children with JIA. Clinical response to methotrexate was evaluated as clinical remission stable for a 6-month period, as ACRPed score and as change in Juvenile Arthritis Disease score. The most relevant SNPs for each gene considered were assayed on patients' DNA. ITPA activity was measured in patients' erythrocytes. Sixty-nine patients with JIA were analyzed: 52.2 % responded to therapy (ACRPed70 score), while 37.7 % reached clinical remission stable for 6 months. ATIC rs2372536 GG genotype was associated with improved clinical remission (adjusted p value = 0.0090). For ITPA, rs1127354 A variant was associated with reduced clinical remission: (adjusted p value = 0.028); this association was present even for patients with wild-type ITPA and low ITPA activity. These preliminary results indicate that genotyping of ATIC rs2372536 and ITPA rs1127354 variants or measuring ITPA activity could be useful to predict methotrexate response in children with JIA after validation by further prospective studies on a larger patient cohort.

Treatment of nonneovascular idiopathic macular telangiectasia type 2 with intravitreal ranibizumab: results of a phase II clinical trial.

PubMed

Toy, Brian C; Koo, Euna; Cukras, Catherine; Meyerle, Catherine B; Chew, Emily Y; Wong, Wai T

2012-05-01

To evaluate the safety and preliminary efficacy of intravitreal ranibizumab for nonneovascular idiopathic macular telangiectasia Type 2. Single-center, open-label Phase II clinical trial enrolling five participants with bilateral nonneovascular idiopathic macular telangiectasia Type 2. Intravitreal ranibizumab (0.5 mg) was administered every 4 weeks in the study eye for 12 months with the contralateral eye observed. Outcome measures included changes in best-corrected visual acuity, area of late-phase leakage on fluorescein angiography, and retinal thickness on optical coherence tomography. The study treatment was well tolerated and associated with few adverse events. Change in best-corrected visual acuity at 12 months was not significantly different between treated study eyes (0.0 ± 7.5 letters) and control fellow eyes (+2.2 ± 1.9 letters). However, decreases in the area of late-phase fluorescein angiography leakage (-33 ± 20% for study eyes, +1 ± 8% for fellow eyes) and in optical coherence tomography central subfield retinal thickness (-11.7 ± 7.0% for study eyes and -2.9 ± 3.5% for fellow eyes) were greater in study eyes compared with fellow eyes. Despite significant anatomical responses to treatment, functional improvement in visual acuity was not detected. Intravitreal ranibizumab administered monthly over a time course of 12 months is unlikely to provide a general and significant benefit to patients with nonneovascular idiopathic macular telangiectasia Type 2.

Bacillus coagulans: a viable adjunct therapy for relieving symptoms of rheumatoid arthritis according to a randomized, controlled trial

PubMed Central

2010-01-01

Background Lactic acid-producing bacteria (LAB) probiotics demonstrate immunomodulating and anti-inflammatory effects and the ability to lessen the symptoms of arthritis in both animals and humans. This randomized, double-blind, placebo-controlled, parallel-design, clinical pilot trial was conducted to evaluate the effects of the LAB probiotic preparation, Bacillus coagulans GBI-30, 6086, on symptoms and measures of functional capacity in patients with rheumatoid arthritis (RA) in combination with pharmacological anti-arthritic medications. Methods Forty-five adult men and women with symptoms of RA were randomly assigned to receive Bacillus coagulans GBI-30, 6086 or placebo once a day in a double-blind fashion for 60 days in addition to their standard anti-arthritic medications. Arthritis activity was evaluated by clinical examination, the American College of Rheumatology (ACR) criteria, the Stanford Health Assessment Questionnaire Disability Index (HAQ-DI), and laboratory tests for erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Results Subjects who received Bacillus coagulans GBI-30, 6086 experienced borderline statistically significant improvement in the Patient Pain Assessment score (P = .052) and statistically significant improvement in Pain Scale (P = .046) vs placebo. Compared with placebo, Bacillus coagulans GBI-30, 6086 treatment resulted in greater improvement in patient global assessment and self-assessed disability; reduction in CRP; as well as the ability to walk 2 miles, reach, and participate in daily activities. There were no treatment-related adverse events reported throughout this study. Conclusions Results of this pilot study suggest that adjunctive treatment with Bacillus coagulans GBI-30, 6086 LAB probiotic appeared to be a safe and effective for patients suffering from RA. Because of the low study population size, larger trials are needed to verify these results. Trial registration ACTRN12609000435280 PMID:20067641

Chuanhu Anti-Gout Mixture versus Colchicine for Acute Gouty Arthritis: A Randomized, Double-Blind, Double-Dummy, Non-Inferiority Trial

PubMed Central

Wang, YanGang; Wang, Luan; Li, EnZe; Li, Yang; Wang, ZhongChao; Sun, XiaoFang; Yu, XiaoLong; Ma, Lin; Wang, YunLong; Wang, YouXin

2014-01-01

Background The Chuanhu anti-gout mixture has been used for many years in the treatment of gout in Chinese Traditional Medicine, and current methods for treatments for acute gouty arthritis have been either less effective or have had serious side effects. Methods In this 12-week, double-blind, double-dummy, non-inferiority study, outpatient individuals with newly diagnosed acute gouty arthritis were randomly assigned to receive Chuanhu anti-gout mixture or colchicine. Both the study investigators and the participants were masked to the treatment assignments. The primary outcome was the recurrence rate of acute gouty arthritis, and the secondary outcomes were changes in white blood cells (WHC) and C-reactive protein (CRP). This trial is registered at ISRCTN.org as trial ISRCTN65219941. Results A total of 176 patients were randomly assigned to receive either the Chuanhu anti-gout mixture or Colchicine. The overall recurrence rates in the Chuanhu anti-gout mixture group (CH group) and the Colchicine group (Col group) were 12.50% vs 14.77% (difference -2.22%, 95% confidence interval (95% CI): -10.78%~6.23%), meeting the predefined non-inferiority criterion of 15%, as did the data for WHC and CRP. The incidence of adverse events (mainly diarrhea) was less in the Col group than in the CH group (2.27% vs 28.41%, 95% CI 0.01~0.26). In addition, changes in blood uric acid, alanine aminotransferase, aspartate aminotransferase and creatinine in the CH group were significantly larger compared to those in the Col group (P<0.05). Conclusions The Chuanhu anti-gout mixture was non-inferior to colchicine for the treatment of acute gouty arthritis. The study suggested that the Chuanhu anti-gout mixture can be considered an alternative choice for the treatment of acute gouty arthritis because of its lower incidence of adverse events and its protection of kidney and renal function. PMID:25013367

Web-based rehabilitation interventions for people with rheumatoid arthritis: A systematic review.

PubMed

Srikesavan, Cynthia; Bryer, Catherine; Ali, Usama; Williamson, Esther

2018-01-01

Background Rehabilitation approaches for people with rheumatoid arthritis include joint protection, exercises and self-management strategies. Health interventions delivered via the web have the potential to improve access to health services overcoming time constraints, physical limitations, and socioeconomic and geographic barriers. The objective of this review is to determine the effects of web-based rehabilitation interventions in adults with rheumatoid arthritis. Methods Randomised controlled trials that compared web-based rehabilitation interventions with usual care, waiting list, no treatment or another web-based intervention in adults with rheumatoid arthritis were included. The outcomes were pain, function, quality of life, self-efficacy, rheumatoid arthritis knowledge, physical activity and adverse effects. Methodological quality was assessed using the Cochrane Risk of Bias tool and quality of evidence with the Grading of Recommendations Assessment, Development and Evaluation approach. Results Six source documents from four trials ( n = 567) focusing on self-management, health information or physical activity were identified. The effects of web-based rehabilitation interventions on pain, function, quality of life, self-efficacy, rheumatoid arthritis knowledge and physical activity are uncertain because of the very low quality of evidence mostly from small single trials. Adverse effects were not reported. Conclusion Large, well-designed trials are needed to evaluate the clinical and cost-effectiveness of web-based rehabilitation interventions in rheumatoid arthritis.

Achieving Consensus on Total Joint Replacement Trial Outcome Reporting Using the OMERACT Filter: Endorsement of the Final Core Domain Set for Total Hip and Total Knee Replacement Trials for Endstage Arthritis.

PubMed

Singh, Jasvinder A; Dowsey, Michelle M; Dohm, Michael; Goodman, Susan M; Leong, Amye L; Scholte Voshaar, Marieke M J H; Choong, Peter F

2017-11-01

Discussion and endorsement of the OMERACT total joint replacement (TJR) core domain set for total hip replacement (THR) and total knee replacement (TKR) for endstage arthritis; and next steps for selection of instruments. The OMERACT TJR working group met at the 2016 meeting at Whistler, British Columbia, Canada. We summarized the previous systematic reviews, the preliminary OMERACT TJR core domain set and results from previous surveys. We discussed preliminary core domains for TJR clinical trials, made modifications, and identified challenges with domain measurement. Working group participants (n = 26) reviewed, clarified, and endorsed each of the inner and middle circle domains and added a range of motion domain to the research agenda. TJR were limited to THR and TKR but included all endstage hip and knee arthritis refractory to medical treatment. Participants overwhelmingly endorsed identification and evaluation of top instruments mapping to the core domains (100%) and use of subscales of validated multidimensional instruments to measure core domains for the TJR clinical trial core measurement set (92%). An OMERACT core domain set for hip/knee TJR trials has been defined and we are selecting instruments to develop the TJR clinical trial core measurement set to serve as a common foundation for harmonizing measures in TJR clinical trials.

Spinal Manipulative Therapy for Adolescent Idiopathic Scoliosis: A Systematic Review.

PubMed

Théroux, Jean; Stomski, Norman; Losco, Christine Dominique; Khadra, Christelle; Labelle, Hubert; Le May, Sylvie

The purpose of this study was to perform a systematic review of clinical trials of spinal manipulative therapy for adolescent idiopathic scoliosis. Search strategies were developed for PubMed, CINHAL, and CENTRAL databases. Studies were included through June 2016 if they were prospective trials that evaluated spinal manipulative therapy (eg, chiropractic, osteopathic, physical therapy) for adolescent idiopathic scoliosis. Data were extracted and assessed by 2 independent reviewers. Cochrane risk of bias tools were used to assess the quality of the included studies. Data were reported qualitatively because heterogeneity prevented statistical pooling. Four studies satisfied the inclusion criteria and were critically appraised. The findings of the included studies indicated that spinal manipulative therapy might be effective for preventing curve progression or reducing Cobb angle. However, the lack of controls and small sample sizes precluded robust estimation of the interventions' effect sizes. There is currently insufficient evidence to establish whether spinal manipulative therapy may be beneficial for adolescent idiopathic scoliosis. The results of the included studies suggest that spinal manipulative therapy may be a promising treatment, but these studies were all at substantial risk of bias. Further high-quality studies are warranted to conclusively determine if spinal manipulative therapy may be effective in the management of adolescent idiopathic scoliosis. Copyright © 2017. Published by Elsevier Inc.

Macrophage activation syndrome in children with systemic lupus erythematosus and children with juvenile idiopathic arthritis.

PubMed

Bennett, Tellen D; Fluchel, Mark; Hersh, Aimee O; Hayward, Kristen N; Hersh, Adam L; Brogan, Thomas V; Srivastava, Rajendu; Stone, Bryan L; Korgenski, E Kent; Mundorff, Michael B; Casper, T Charles; Bratton, Susan L

2012-12-01

To describe patient demographics, interventions, and outcomes in hospitalized children with macrophage activation syndrome (MAS) complicating systemic lupus erythematosus (SLE) or juvenile idiopathic arthritis (JIA). We performed a retrospective cohort study using data recorded in the Pediatric Health Information System (PHIS) database from October 1, 2006 to September 30, 2010. Participants had International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for MAS and either SLE or JIA. The primary outcome was hospital mortality (for the index admission). Secondary outcomes included intensive care unit (ICU) admission, critical care interventions, and medication use. A total of 121 children at 28 children's hospitals met the inclusion criteria, including 19 children with SLE and 102 children with JIA. The index admission mortality rate was 7% (8 of 121 patients). ICU admission (33%), mechanical ventilation (26%), and inotrope/vasopressor therapy (26%) were common. Compared to children with JIA, those with SLE had a similar mortality rate (6% versus 11%, respectively; exact P = 0.6). More patients with SLE than those with JIA received ICU care (63% versus 27%; P = 0.002), received mechanical ventilation (53% versus 21%; P = 0.003), and had cardiovascular dysfunction (47% versus 23% received inotrope/vasopressor therapy; P = 0.02). Children with SLE and those with JIA received cyclosporine at similar rates, but more children with SLE received cyclophosphamide and mycophenolate mofetil, and more children with JIA received interleukin-1 antagonists. Organ system dysfunction is common in children with rheumatic diseases complicated by MAS, and more organ system support is required in children with underlying SLE than in children with JIA. Current treatment of pediatric MAS varies based on the underlying rheumatic disease. Copyright © 2012 by the American College of Rheumatology.

Measurement of blood calprotectin (MRP-8/MRP-14) levels in patients with juvenile idiopathic arthritis.

PubMed

Bojko, Jaryna

2017-01-01

The aim of the investigation was to compare blood calprotectin (MRP8/14, S100A 8/9) levels in patients with systemic-onset, polyarticular, RF-negative and oligoarticular subtypes of juvenile idiopathic arthritis (JIA), and to explore links between blood calprotectin levels and clinical and laboratory markers of JIA activity. Measurement of calprotectin in blood serum was performed in 160 patients with JIA followed up at Lviv Regional Council Public Institution "Western-Ukrainian Specialised Children's Medical Centre". Seventeen patients with systemic-onset JIA (sJIA) and 49 patients with other JIA subtypes (RF-negative polyarthritis and oligoarthritis) in the active phase of the disease were included in this study. Determination of calprotectin levels in blood serum was performed using EK-MRP8/14 Buhlmann Calprotectin reagents (Buhlmann, Switzerland) by the ELISA method. The results of the investigations showed that blood calprotectin levels were higher in patients with systemic-onset subtype of the disease (median 13,800 ng/ml), and differed significantly from levels in healthy children (median 1,800 ng/ml, p = 0.00002), levels in patients with articular subtypes of JIA (median 2,700 ng/ml, p = 0.000008), and patients with RF-negative polyarthritis (median 3,800 ng/ml, p = 0.003226) and oligoarthritis (median 2,500 ng/ml, p = 0.000009). The highest blood calprotectin levels were found in patients with newly diagnosed sJIA, the median being 32,500 ng/ml (range: 13,800-177,000 ng/ml). Direct correlations were found between blood calprotectin and JADAS 27 activity score ( p = 0.000009), ESR ( p = 0.000079) and CRP ( p = 0.000058). Blood calprotectin level is one of the measures that can be used to confirm the diagnosis of sJIA and to monitor the disease activity and therapy effectiveness.

Is Intra-Articular Steroid Injection to the Temporomandibular Joint for Juvenile Idiopathic Arthritis More Effective and Efficient When Performed With Image Guidance?

PubMed

Resnick, Cory M; Vakilian, Pouya M; Kaban, Leonard B; Peacock, Zachary S

2017-04-01

To compare short-term outcomes and procedure times for intra-articular steroid injection (IASI) to the temporomandibular joint (TMJ) with and without the use of intraoperative image guidance for patients with juvenile idiopathic arthritis (JIA). This is a retrospective study of children with JIA who underwent TMJ IASI at Boston Children's Hospital (Boston, MA). Patients were divided into groups according to IASI technique: 1) "landmark" group if performed by an oral and maxillofacial surgeon using an anatomic landmark technique with no intraoperative image guidance or 2) "image-guided" group if performed by an interventional radiologist using intraoperative ultrasound and computed tomography. Predictor variables included IASI technique (landmark vs image guided), age, gender, JIA subtype, category of medications for arthritis, and presence of family history of autoimmune disease. Outcome variables were changes in patient-reported pain, maximal incisal opening (MIO), synovial enhancement ratio (ER), and total procedure time. Forty-five patients with 71 injected TMJs were included. Twenty-two patients with 36 injected TMJs were in the landmark group and 23 patients with 35 injected joints were in the image-guided group. There were no relevant differences in age, gender, family history of rheumatologic disease, or disease subtype between groups. There were no differences in resolution of pain (P = 1.00), increase in MIO (P = .975), or decrease in ER (P = .492) between groups, but procedure times averaged 49 minutes longer for the image-guided group (P < .008). There were no statistical differences in short-term outcomes, but procedure times were longer for the image-guided group. Although specific indications for the use of image guidance might exist, routine use of this procedure cannot be justified. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Magnetic Resonance Imaging (MRI) of the Knee as an Outcome Measure in Juvenile Idiopathic Arthritis: An OMERACT Reliability Study on MRI Scales.

PubMed

Hemke, Robert; Tzaribachev, Nikolay; Nusman, Charlotte M; van Rossum, Marion A J; Maas, Mario; Doria, Andrea S

2017-08-01

There is increasing evidence that early therapeutic intervention improves longterm joint outcome in juvenile idiopathic arthritis (JIA). Given the existence of highly effective treatments, there is an urgent need for reliable and accurate measures of disease activity and joint damage in JIA. Our objective was to assess the reliability of 2 magnetic resonance imaging (MRI) scoring methods: the Juvenile Arthritis MRI Scoring (JAMRIS) system and the International Prophylaxis Study Group (IPSG) consensus score, for evaluating disease status of the knee in patients with JIA. Four international readers independently scored an MRI dataset of 25 JIA patients with clinical knee involvement. Synovial thickening, joint effusion, bone marrow changes, cartilage lesions, bone erosions, and subchondral cysts were scored using the JAMRIS and IPSG systems. Further, synovial enhancement, infrapatellar fat pad heterogeneity, tendinopathy, and enthesopathy were scored. Interreader reliability was analyzed by using the generalized κ, ICC, and the smallest detectable difference (SDD). ICC regarding interreader reliability ranged from 0.33 (95% CI 0.12-0.52, SDD = 0.29) for enthesopathy up to 0.95 (95% CI 0.92-0.97, SDD = 3.19) for synovial thickening. Good interreader reliability was found concerning joint effusion (ICC 0.93, 95% CI 0.89-0.95, SDD = 0.51), synovial enhancement (ICC 0.90, 95% CI 0.85-0.94, SDD = 9.85), and bone marrow changes (ICC 0.87, 95% CI 0.80-0.92, SDD = 10.94). Moderate to substantial reliability was found concerning cartilage lesions and bone erosions (ICC 0.55-0.72, SDD 1.41-13.65). The preliminary results are promising for most of the scored JAMRIS and IPSG items. However, further refinement of the scoring system is warranted for unsatisfactorily reliable items such as bone erosions, cartilage lesions, and enthesopathy.

Effects on growth and body composition of growth hormone treatment in children with juvenile idiopathic arthritis requiring steroid therapy.

PubMed

Simon, Dominique; Lucidarme, Nadine; Prieur, Anne-Marie; Ruiz, Jean Charles; Czernichow, Paul

2003-11-01

Decreased growth velocity and abnormal body composition including severe osteoporosis are common in glucocorticoid-treated patients with juvenile idiopathic arthritis (JIA). We evaluated the effects of recombinant human growth hormone (GH) given for 3 years on growth velocity, height standard deviation score (SDS), and body composition, together with potential adverse effects on glucose tolerance. Thirteen patients received GH (0.46 mg/kg/week) for 3 years. Body composition was assessed by dual-energy x-ray absorptiometry and glucose tolerance by annual oral glucose tolerance tests. Median growth velocity increased from 2.1 to 6.0 cm/year (p = 0.002) in the first year and remained higher than baseline in the second year of treatment. Height SDS did not change significantly (-4.6 SDS at baseline vs -4.3 SDS at study completion), but the growth response varied markedly across patients. Compared with baseline, lean mass increased by 33%, fat mass remained stable, and lumbar bone mineral density increased by 36.6%. Transient glucose intolerance developed in 6 patients, but glycosylated hemoglobin concentrations did not change significantly and diabetes mellitus did not occur. Treatment with GH restored linear growth without inducing catch-up growth, significantly improved body composition, and prevented further bone loss. Prolonged followup is needed to assess the benefits of GH and longterm consequences of hyperinsulinism.

Intra-articular corticoid injection induces circulating glucocorticoid bioactivity and systemic immune activation in juvenile idiopathic arthritis.

PubMed

Rintamäki, H; Tamm, K; Vaarala, O; Sidoroff, M; Honkanen, V; Raivio, T; Jänne, Oa; Kolho, K-L

2011-01-01

To study the systemic effects of intra-articular (IA) glucocorticoid (GC) injections in juvenile idiopathic arthritis (JIA). The study group comprised 21 JIA patients being treated with IA methylprednisolone [MP (n = 15) or MP plus triamcinolone hexacetonide (THA) (n = 6)] prescribed on clinical indications. The systemic effect of MP was assessed by measuring circulating glucocorticoid bioactivity (GBA) with a recombinant cell transactivation assay 7 and 24 h after the IA injections, and after 2 months. The systemic immunological responses were studied with a novel assay for testing patient serum-induced changes in the secretion of interferon (IFN)-γ and interleukin (IL)-5 from target cells. Administration of IA GC induced serum GBA (p = 0.001) and suppressed circulating cortisol levels (p = 0.002) 7 h after the injection. Serum withdrawn 24 h after the IA injection induced less IL-5 secretion from mitogen-activated target cells when compared with pre-treatment sera (p = 0.036). This decrease in target cell T helper (Th)2 response (IL-5) was MP dose related (r = -0.550, p = 0.018). High IL-5 secretion from target cells prior to the IA injections was associated with good clinical outcome at 2 months, seen as a low number of active (p = 0.044) and restricted joints (p = 0.049). IA GC injections have systemic effects that are reflected in the serum as an immediate elevation of GBA, a decrease of endogenous cortisol as well as a suppressive effect of patient serum on target cell IL-5 secretion. These systemic effects may play a role in the attenuation of disease activity.

Consensus-based recommendations for the management of uveitis associated with juvenile idiopathic arthritis: the SHARE initiative.

PubMed

Constantin, Tamas; Foeldvari, Ivan; Anton, Jordi; de Boer, Joke; Czitrom-Guillaume, Severine; Edelsten, Clive; Gepstein, Raz; Heiligenhaus, Arnd; Pilkington, Clarissa A; Simonini, Gabriele; Uziel, Yosef; Vastert, Sebastian J; Wulffraat, Nico M; Haasnoot, Anne-Mieke; Walscheid, Karoline; Pálinkás, Annamária; Pattani, Reshma; Györgyi, Zoltán; Kozma, Richárd; Boom, Victor; Ponyi, Andrea; Ravelli, Angelo; Ramanan, Athimalaipet V

2018-03-28

In 2012, a European initiative called S ingle Hub and Access point for pediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases. Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children and uveitis is possibly its most devastating extra-articular manifestation. Evidence-based guidelines are sparse and management is mostly based on physicians' experience. Consequently, treatment practices differ widely, within and between nations. To provide recommendations for the diagnosis and treatment of JIA-associated uveitis. Recommendations were developed by an evidence-informed consensus process using the European League Against Rheumatism standard operating procedures. A committee was constituted, consisting of nine experienced paediatric rheumatologists and three experts in ophthalmology from Europe. Recommendations derived from a validated systematic literature review were evaluated by an Expert Committee and subsequently discussed at two consensus meetings using nominal group techniques. Recommendations were accepted if >80% agreement was reached (including all three ophthalmologists). In total, 22 recommendations were accepted (with >80% agreement among experts): 3 on diagnosis, 5 on disease activity measurements, 12 on treatment and 2 on future recommendations. The SHARE initiative aims to identify best practices for treatment of patients suffering from JIA-associated uveitis. Within this remit, recommendations for the diagnosis and treatment of JIA-associated uveitis have been formulated by an evidence-informed consensus process to suggest a standard of care for JIA-associated uveitis patients throughout Europe. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Disease-modifying antirheumatic drugs other than methotrexate in rheumatoid arthritis and seronegative arthritis.

PubMed

Nandi, Pradip; Kingsley, Gabrielle H; Scott, David L

2008-05-01

To outline recent research findings with nonmethotrexate disease-modifying antirheumatic drugs in rheumatoid arthritis and seronegative arthritis spanning systematic reviews, randomized controlled trials, observational clinical practice trials and assessments of adverse effects. Systematic reviews show no important differences between methotrexate, leflunomide and sulfasalazine monotherapies; early disease-modifying antirheumatic drug therapy reduces erosive progression. Observational studies show that nonmethotrexate disease-modifying antirheumatic drugs are widely prescribed; their usage has increased in the biologic era. A systemic review also showed patients who failed monotherapy benefited from disease-modifying antirheumatic drug combinations without excess toxicity. Randomized controlled trials of intensive initial disease-modifying antirheumatic drug combinations showed they reduce synovitis and erosive damage, especially when used with steroids. The subsequent sequence of disease-modifying antirheumatic drugs and the value of changing disease-modifying antirheumatic drug monotherapies or stepping-up to combination disease-modifying antirheumatic drugs are, however, unresolved. The adverse risks of nonmethotrexate disease-modifying antirheumatic drugs have been evaluated, including infections and lung disease; patient-related risks seem more important than drug-related risks, though several disease-modifying antirheumatic drugs increase both types of adverse reactions. Two limitations of nonmethotrexate disease-modifying antirheumatic drugs are reduced impact on comorbidities like cardiovascular disease and reduced patient and clinician preferences for these treatments. Nonmethotrexate disease-modifying antirheumatic drugs are effective, relatively well tolerated and widely used. Their role in intensive treatment strategies in early rheumatoid arthritis appears of crucial importance.

Tumor necrosis factor-α -308 A/G gene polymorphism in children with juvenile idiopathic arthritis: relation to disease activity, damage, and functional status.

PubMed

El Gazzar, Iman I; Fathy, Hanan M; Gheita, Tamer A; Nour El-Din, Abeer M; Rasheed, Enas Abdel; Bassyouni, Rasha H; Kenawy, Sanaa A

2017-08-01

The study aims to evaluate the clinical significance of serum levels of tumor necrosis factor alpha (TNF-α) and -308 A/G promoter polymorphism in juvenile idiopathic arthritis (JIA) patients and find any association to the subsets, clinical and laboratory features, disease activity, and damage as well as functional disability. Forty-eight JIA children and 30 controls were included in the present study. Juvenile arthritis disease activity score in 27 joints (JADAS-27) was calculated, juvenile arthritis damage index (JADI) was assessed, and Childhood Health Assessment Questionnaire (CHAQ) measured the functional status. Serum TNF-α was assayed by ELISA and gene (-308) promoter polymorphism was determined by polymerase chain reaction. The 48 JIA children (mean age 11.5 ± 2.8 years) were 13 systemic, 17 oligoarticular, and 18 polyarticular onset. The serum TNF-α was significantly higher in patients (90.4 ± 6.3 ng/ml) compared to control (3.5 ± 2.6 ng/ml) (p < 0.0001) with a tendency to be higher in the polyarticular subtype. All controls had TNF-α -308 GG alleles. The frequency of GG genotype tended to be higher in systemic onset compared to oligoarticular and polyarticular subtypes. The serum TNF-α significantly correlated with JADAS-27 (r = 0.32, p = 0.03) and CHAQ (r = 0.37, p = 0.01) and negatively with the presence of GG alleles (r = -0.48, p = 0.001). The GG alleles were significantly negatively associated with C-reactive protein (r = -0.32, p = 0.03) with a tendency to negatively correlate with JADAS-27, CHAQ, and JADI-extrarticular (r = -0.28, p = 0.06; r = -0.25, p = 0.09 and r = -0.25, p = 0.09, respectively). There is evidence of a possible influence of the -308 SNP promoter position on the production of TNF-α, the severity of JIA which may consequently influence the response to anti-TNF-α treatment.

The effect of positive family history of autoimmunity in juvenile idiopathic arthritis characteristics; a case control study.

PubMed

Khani, Mehdi; Ziaee, Vahid; Moradinejad, Mohamad-Hassan; Parvaneh, Nima

2013-10-01

To compare Juvenile Idiopathic Arthritis (JIA) patients with and without family history of autoimmune disease with respect to clinical features and laboratory data. Sixteen JIA patients with family history of autoimmune disease were identified during study, 32 patients were chosen for comparative group from referred patients to the rheumatology clinic according to the date of referral. Two groups were compared with respect to age of onset, sex, subtype, disease activity, duration of active disease and laboratory variables. The age of onset was significantly lower in JIA patients with family history of autoimmunity (4.7 years vs. 7.0 years; P=0.02), polyarthicular subtype was more frequent in patients with positive family history (50% vs.25%; P=0.04) most of JIA patients with positive family history were in the active phase at the time of study (64% vs 25%; P=0.02) and had a longer duration of active disease (21.0 months vs 12.3 months; P=0.04). Patients with positive family history had more positive ANA (43.5%% vs 12.5%; P=0.01) and also more positive ADA (75% vs 20.8%; P=0.002). Two groups were similar according to sex, and other laboratory variables. JIA patients with family history of autoimmune disease seem to have a more severe disease than patients without such family history, they are younger at the onset, and have mostly poyarthicular subtype. They also have more ANA and ADA positivity. These findings are different from familial JIA case-control studies according to active disease duration, subtype, and ANA positivity.

Ultrasound-guided steroid tendon sheath injections in juvenile idiopathic arthritis: a 10-year single-center retrospective study.

PubMed

Peters, Shannon E; Laxer, Ronald M; Connolly, Bairbre L; Parra, Dimitri A

2017-04-11

The aims of this study were to: (a) Identify tendon sheaths most commonly treated with steroid injections in a pediatric patient population with Juvenile Idiopathic Arthritis (JIA); (b) Describe technical aspects of the procedure; (c) Characterize sonographic appearance of tenosynovitis in JIA; (d) Assess agreement between clinical request and sites injected. This was a 10 year single-center retrospective study (May 2006-April 2016) of patients with JIA referred by Rheumatology for ultrasound-guided tendon sheath injections. Patient demographics, clinical referral information, sonographic appearance of the tendon sheaths and technical aspects of the procedure were analyzed. There were 308 procedures of 244 patients (75% female, mean age 9.6 years) who underwent a total of 926 tendon sheath injections. Ankle tendons were most commonly injected (84.9%), specifically the tendon sheaths of tibialis posterior (22.3%), peroneus longus (20%) and brevis (19.7%). The majority of treated sites (91.9%) showed peritendinous fluid and sheath thickening on ultrasound. There were 2 minor intra-procedure complications without sequelae. A good agreement between clinical request and sites injected was observed. Ultrasound-guided tendon sheath injections with steroids are used frequently to treat patients with JIA. It is a safe intervention with a high technical success rate. The ankle region, specifically the medial compartment, is the site most commonly injected in this group of patients. The most common sonographic finding is peritendinous fluid and sheath thickening. These findings might assist clinicians and radiologists to characterize and more effectively manage tenosynovitis in patients with JIA.

Treatment choices of paediatric rheumatologists for juvenile idiopathic arthritis: etanercept or adalimumab?

PubMed

Anink, Janneke; Otten, Marieke H; Gorter, Simone L; Prince, Femke H M; van Rossum, Marion A J; van den Berg, J Merlijn; van Pelt, Philomine A; Kamphuis, Sylvia; Brinkman, Danielle M C; Swen, Wijnand A A; Swart, Joost F; Wulffraat, Nico M; Dolman, Koert M; Koopman-Keemink, Yvonne; Hoppenreijs, Esther P A H; Armbrust, Wineke; ten Cate, Rebecca; van Suijlekom-Smit, Lisette W A

2013-09-01

To evaluate differences in baseline characteristics between etanercept- and adalimumab-treated JIA patients and to reveal factors that influence the choice between these TNF inhibitors, which are considered equally effective in the recent ACR recommendations for JIA treatment. Biologic-naïve JIA patients with active arthritis who started treatment with adalimumab or etanercept between March 2008 and December 2011 were selected from the Dutch Arthritis and Biologicals in Children register. Baseline characteristics were compared. Focus group interviews with paediatric rheumatologists were performed to evaluate factors determining treatment choices. A total of 193 patients started treatment with etanercept and 21 with adalimumab. Adalimumab-treated patients had longer disease duration prior to the start of biologics (median 5.7 vs 2.0 years) and more often a history of uveitis (71% vs 4%). Etanercept-treated patients had more disability at baseline (median Childhood Health Assessment Questionnaire score 1.1 vs 0.4) and more active arthritis (median number of active joints 6 vs 4). The presence of uveitis was the most important factor directing the choice towards adalimumab. Factors specific for the paediatric population-such as painful adalimumab injections-as well as the physician's familiarity with the drug accounted for the preference for etanercept. Although the two TNF inhibitors are considered equally effective, in daily practice etanercept is most often prescribed; adalimumab is mainly preferred when uveitis is present. In choosing the most suitable biologic treatment, paediatric rheumatologists take into account drug and patient factors, considering newly published data and cautiously implementing this into daily care.

Sclerotherapy of idiopathic hydroceles and epididymal cysts: a historical comparison trial of 5% phenol versus tetracycline.

PubMed

East, J M; DuQuesnay, D

2007-12-01

Operating time for idiopathic hydroceles and epididymal cysts is scarce as these conditions compete with an increasing caseload of more consequential surgical disease. Therapy is often relegated to repeated aspiration. Sclerotherapy appears to be effective in a majority of published trials, but comparative effectiveness, efficacy and safety of most agents, including phenol versus tetracycline, has not been established A deliberate strategy of re-treatment until cure is not universally practised, with surgery still being offered after single-treatment failures. Two trials, the first consisting of 53 scrotal cysts treated with 5% phenol-in-water and the second, 42 cysts treated with tetracycline, are compared for effectiveness, efficacy and safety of sclerotherapy per se and of re-treatment. Intention-to-treat analysis yields similar cure rates (no re-accumulation three months after last injection) for phenol and tetracycline (83% and 81% respectively, p = 0.8). Per-protocol analysis also yields similar cure rates (100% and 97% respectively, p = 0.26) and mean number of injections to cure (1.34 and 1.12 respectively, p = 0.069), with range 1-4 and 1-3 respectively. Severe pain following tetracycline injection required administration of pre-injection cord block. Other complications occurred equally (25% and 25.7% respectively, p = 0.94) and were trivial except for one case of chronic haematocele treated by orchiectomy in the tetracycline group. Phenol (5%) and tetracycline are equally efficacious sclerosants for idiopathic scrotal cysts, achieving almost 100% cure with re-treatment and matching the efficacy of surgery. Concern about post-treatment fertility applies equally to surgery and demands informed consent for both modalities.

The frequency and outcome of uveitis in patients with newly diagnosed juvenile idiopathic arthritis in two 4-year cohorts from 1990-1993 and 2000-2003.

PubMed

Kotaniemi, Kaisu; Sihto-Kauppi, Kristiina; Salomaa, Pirjo; Säilä, Hanna; Ristolainen, Leena; Kauppi, Markku

2014-01-01

To retrospectively compare the frequency and outcome of uveitis between two cohorts of patients with newly-onset juvenile idiopathic arthritis (JIA) separated by a 10 year interval. The diagnosis of JIA was made in 239 patients in 1990-1993 and in 240 patients in 2000-2003 by paediatric rheumatologists at the Rheumatism Foundation Hospital, Heinola, Finland. An ophthalmologist examined all the patients regularly and diagnosed uveitis. The demographics of the patients, type of JIA, frequency, medical treatment and outcome of uveitis were documented. The main outcome measures were the frequency and outcome of uveitis, the number of complications and the best corrected visual acuity (BCVA), need of corticosteroids and other immunosuppressive treatment. The frequency of uveitis was higher (25% vs. 18%) in the earlier cohort. The visual outcome was ≥0.5 in all JIA-uveitis patients except one in the earlier cohort. Complications were fewer (21% vs. 35%) and uveitis was milder according to the Standardisation of Uveitis Nomenclature (SUN) criteria in the later cohort. Remission of uveitis (33% vs. 42%) and arthritis (20% vs. 23%) in JIA-uveitis patients was similar in both cohorts after a follow-up of 6.6 and 5.9 years, respectively. Systemic corticosteroids were more commonly used (25% vs. 7%) in JIA-uveitis patients of the earlier cohort but the use of methotrexate was equal in both cohorts (65% vs. 67%). In this study with early and aggressive treatment and close monitoring the outcome of JIA-uveitis patients was favourable and visual loss was avoided in most cases.

[Idiopathic facial paralysis in children].

PubMed

Achour, I; Chakroun, A; Ayedi, S; Ben Rhaiem, Z; Mnejja, M; Charfeddine, I; Hammami, B; Ghorbel, A

2015-05-01

Idiopathic facial palsy is the most common cause of facial nerve palsy in children. Controversy exists regarding treatment options. The objectives of this study were to review the epidemiological and clinical characteristics as well as the outcome of idiopathic facial palsy in children to suggest appropriate treatment. A retrospective study was conducted on children with a diagnosis of idiopathic facial palsy from 2007 to 2012. A total of 37 cases (13 males, 24 females) with a mean age of 13.9 years were included in this analysis. The mean duration between onset of Bell's palsy and consultation was 3 days. Of these patients, 78.3% had moderately severe (grade IV) or severe paralysis (grade V on the House and Brackmann grading). Twenty-seven patients were treated in an outpatient context, three patients were hospitalized, and seven patients were treated as outpatients and subsequently hospitalized. All patients received corticosteroids. Eight of them also received antiviral treatment. The complete recovery rate was 94.6% (35/37). The duration of complete recovery was 7.4 weeks. Children with idiopathic facial palsy have a very good prognosis. The complete recovery rate exceeds 90%. However, controversy exists regarding treatment options. High-quality studies have been conducted on adult populations. Medical treatment based on corticosteroids alone or combined with antiviral treatment is certainly effective in improving facial function outcomes in adults. In children, the recommendation for prescription of steroids and antiviral drugs based on adult treatment appears to be justified. Randomized controlled trials in the pediatric population are recommended to define a strategy for management of idiopathic facial paralysis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Randomised clinical trial: gastrointestinal events in arthritis patients treated with celecoxib, ibuprofen or naproxen in the PRECISION trial.

PubMed

Yeomans, N D; Graham, D Y; Husni, M E; Solomon, D H; Stevens, T; Vargo, J; Wang, Q; Wisniewski, L M; Wolski, K E; Borer, J S; Libby, P; Lincoff, A M; Lüscher, T F; Bao, W; Walker, C; Nissen, S E

2018-06-01

To evaluate GI safety of celecoxib compared with 2 nonselective (ns) NSAIDs, as a secondary objective of a large trial examining multiorgan safety. This randomised, double-blind controlled trial analysed 24 081 patients. Osteoarthritis or rheumatoid arthritis patients, needing ongoing NSAID treatment, were randomised to receive celecoxib 100-200 mg b.d., ibuprofen 600-800 mg t.d.s. or naproxen 375-500 mg b.d. plus esomeprazole, and low-dose aspirin or corticosteroids if already prescribed. Clinically significant GI events (CSGIE-bleeding, obstruction, perforation events from stomach downwards or symptomatic ulcers) and iron deficiency anaemia (IDA) were adjudicated blindly. Mean treatment and follow-up durations were 20.3 and 34.1 months. While on treatment or 30 days after, CSGIE occurred in 0.34%, 0.74% and 0.66% taking celecoxib, ibuprofen and naproxen. Hazard ratios (HR) were 0.43 (95% CI 0.27-0.68, P = 0.0003) celecoxib vs ibuprofen and 0.51 (0.32-0.81, P = 0.004) vs naproxen. There was also less IDA on celecoxib: HR 0.43 (0.27-0.68, P = 0.0003) vs ibuprofen; 0.40 (0.25-0.62, P < 0.0001) vs naproxen. Even taken with low-dose aspirin, fewer CSGIE occurred on celecoxib than ibuprofen (HR 0.52 [0.29-0.94], P = 0.03), and less IDA vs naproxen (0.42 [0.23-0.77, P = 0.005]). Corticosteroid use increased total GI events and CSGIE. H. pylori serological status had no influence. Arthritis patients taking NSAIDs plus esomeprazole have infrequent clinically significant gastrointestinal events. Co-prescribed with esomeprazole, celecoxib has better overall GI safety than ibuprofen or naproxen at these doses, despite treatment with low-dose aspirin or corticosteroids. © 2018 John Wiley & Sons Ltd.

Idiopathic Pulmonary Fibrosis: Clinically Meaningful Primary Endpoints in Phase 3 Clinical Trials

PubMed Central

Collard, Harold R.; Anstrom, Kevin J.; Flaherty, Kevin R.; Fleming, Thomas R.; King, Talmadge E.; Martinez, Fernando J.; Brown, Kevin K.

2012-01-01

Definitive evidence of clinical efficacy in a Phase 3 trial is best shown by a beneficial impact on a clinically meaningful endpoint—that is, an endpoint that directly measures how a patient feels (symptoms), functions (the ability to perform activities in daily life), or survives. In idiopathic pulmonary fibrosis (IPF), we believe the endpoints that best meet these criteria are all-cause mortality and all-cause nonelective hospitalization. There are no validated measures of symptoms or broader constructs such as health status or funtional status in IPF. A surrogate endpoint is defined as an indirect measure that is intended to substitute for a clinically meaningful endpoint. Surrogate endpoints can be appropriate outcome measures if validated. However, validation requires substantial evidence that the effect of an intervention on a clinically meaningful endpoint is reliably predicted by the effect of an intervention on the surrogate endpoint. For patients with IPF, there are currently no validated surrogate endpoints. PMID:22505745

A Multicenter Randomized Controlled Trial of Rituximab versus Cyclosporine in the Treatment of Idiopathic Membranous Nephropathy (MENTOR).

PubMed

Fervenza, Fernando C; Canetta, Pietro A; Barbour, Sean J; Lafayette, Richard A; Rovin, Brad H; Aslam, Nabeel; Hladunewich, Michelle A; Irazabal, Maria V; Sethi, Sanjeev; Gipson, Debbie S; Reich, Heather N; Brenchley, Paul; Kretzler, Matthias; Radhakrishnan, Jai; Hebert, Lee A; Gipson, Patrick E; Thomas, Leslie F; McCarthy, Ellen T; Appel, Gerald B; Jefferson, J Ashley; Eirin, Alfonso; Lieske, John C; Hogan, Marie C; Greene, Eddie L; Dillon, John J; Leung, Nelson; Sedor, John R; Rizk, Dana V; Blumenthal, Samuel S; Lasic, Lada B; Juncos, Luis A; Green, Dollie F; Simon, James; Sussman, Amy N; Philibert, David; Cattran, Daniel C

2015-01-01

Idiopathic membranous nephropathy remains the leading cause of nephrotic syndrome in Caucasian adults. Immunosuppressive therapy with cyclosporine (CSA) is often successful in reducing proteinuria, but its use is associated with a high relapse rate. Rituximab, a monoclonal antibody that specifically targets CD20 on the surface of B-cells, is effective in achieving a complete remission of proteinuria in patients with idiopathic membranous nephropathy. However, whether rituximab is as effective as CSA in inducing and maintaining complete or partial remission of proteinuria in these patients is unknown. The membranous nephropathy trial of rituximab (MENTOR) hypothesizes that B-cell targeting with rituximab is non-inferior to CSA in inducing long-term remission of proteinuria. Patients with idiopathic membranous nephropathy, proteinuria ≥5 g/24 h, and a minimum of 3 months of Angiotensin-II blockade will be randomized into a 12-month treatment period with i.v. rituximab, 1,000 mg (2 infusions, 14 days apart; repeated at 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months) or oral CSA 3.5-5 mg/kg/day for 6 months (continued for another 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months). The efficacy of treatment will be assessed by the remission status (based on changes in proteinuria) at 24 months from randomization. Patient safety will be assessed via collection of adverse event data and evaluation of pre- and posttreatment laboratory data. At the 6-month post-randomization visit, patients who have been randomized to either CSA or rituximab but who do not have a reduction in proteinuria ≥25% (confirmed on repeat measurements within 2 weeks) will be considered treatment failures and exit the study. This study will test for the first time whether treatment with rituximab is non-inferior to CSA in inducing long-term remission (complete or partial) of proteinuria in patients with idiopathic

Design of the INPULSIS™ trials: two phase 3 trials of nintedanib in patients with idiopathic pulmonary fibrosis.

PubMed

Richeldi, Luca; Cottin, Vincent; Flaherty, Kevin R; Kolb, Martin; Inoue, Yoshikazu; Raghu, Ganesh; Taniguchi, Hiroyuki; Hansell, David M; Nicholson, Andrew G; Le Maulf, Florence; Stowasser, Susanne; Collard, Harold R

2014-07-01

Nintedanib is in clinical development as a treatment for idiopathic pulmonary fibrosis (IPF). Data from the Phase II TOMORROW study suggested that nintedanib 150 mg twice daily had clinical benefits with an acceptable safety profile. The INPULSIS™ trials are replicate Phase III, randomized, double-blind, studies comparing the efficacy and safety of nintedanib 150 mg twice daily with placebo in patients with IPF. Eligible patients were aged ≥40 years with a diagnosis of IPF within 5 years before randomization who had undergone a chest high-resolution computed tomography (HRCT) scan within 1-year before screening, and who had a forced vital capacity (FVC) of ≥50% predicted and a diffusing capacity for carbon monoxide of 30-79% predicted. Participants were randomized 3:2 to receive nintedanib or placebo for 52 weeks. The primary endpoint is the annual rate of decline in FVC. The key secondary endpoints are change from baseline in the total score on the St. George's Respiratory Questionnaire (a measure of health-related quality of life) over 52 weeks and time to first acute exacerbation. Enrolment of 1066 patients in 24 countries was completed in September 2012. Results will be reported in the first half of 2014. The INPULSIS™ trials will determine the efficacy of nintedanib in patients with IPF, including its impact on disease progression as defined by decline in FVC, acute exacerbations and health-related quality of life. In addition, they will characterise the adverse event profile of nintedanib in this patient population. Registered at ClinicalTrials.gov (identifiers: NCT01335464 and NCT01335477). Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Update on ibuprofen for rheumatoid arthritis.

PubMed

Ward, J R

1984-07-13

In doses of 1,200 mg/day or more, ibuprofen is as effective as aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of rheumatoid arthritis. The tolerability and safety of ibuprofen are superior to those of aspirin and compare favorably with those of other NSAIDs. Although additional controlled trials are indicated to determine optimal dose, ibuprofen's excellent therapeutic index establishes it as a useful drug in the treatment of rheumatoid arthritis.

2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative.

PubMed

Ravelli, Angelo; Minoia, Francesca; Davì, Sergio; Horne, AnnaCarin; Bovis, Francesca; Pistorio, Angela; Aricò, Maurizio; Avcin, Tadej; Behrens, Edward M; De Benedetti, Fabrizio; Filipovic, Lisa; Grom, Alexei A; Henter, Jan-Inge; Ilowite, Norman T; Jordan, Michael B; Khubchandani, Raju; Kitoh, Toshiyuki; Lehmberg, Kai; Lovell, Daniel J; Miettunen, Paivi; Nichols, Kim E; Ozen, Seza; Pachlopnik Schmid, Jana; Ramanan, Athimalaipet V; Russo, Ricardo; Schneider, Rayfel; Sterba, Gary; Uziel, Yosef; Wallace, Carol; Wouters, Carine; Wulffraat, Nico; Demirkaya, Erkan; Brunner, Hermine I; Martini, Alberto; Ruperto, Nicolino; Cron, Randy Q

2016-03-01

To develop criteria for the classification of macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (JIA). A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of 28 experts was first asked to classify 428 patient profiles as having or not having MAS, based on clinical and laboratory features at the time of disease onset. The 428 profiles comprised 161 patients with systemic JIA-associated MAS and 267 patients with a condition that could potentially be confused with MAS (active systemic JIA without evidence of MAS, or systemic infection). Next, the ability of candidate criteria to classify individual patients as having MAS or not having MAS was assessed by evaluating the agreement between the classification yielded using the criteria and the consensus classification of the experts. The final criteria were selected in a consensus conference. Experts achieved consensus on the classification of 391 of the 428 patient profiles (91.4%). A total of 982 candidate criteria were tested statistically. The 37 best-performing criteria and 8 criteria obtained from the literature were evaluated at the consensus conference. During the conference, 82% consensus among experts was reached on the final MAS classification criteria. In validation analyses, these criteria had a sensitivity of 0.73 and a specificity of 0.99. Agreement between the classification (MAS or not MAS) obtained using the criteria and the original diagnosis made by the treating physician was high (κ = 0.76). We have developed a set of classification criteria for MAS complicating systemic JIA and provided preliminary evidence of its validity. Use of these criteria will potentially improve understanding of MAS in systemic JIA and enhance efforts to discover effective therapies, by ensuring appropriate patient enrollment in studies. © 2015, American College of Rheumatology.

Can we improve the performance and reporting of investigator-initiated clinical trials? Rheumatoid arthritis as an example.

PubMed

Landewé, Robert B M; Smolen, Josef S; Weinblatt, Michael E; Emery, Paul; Dougados, Maxime; Fleischmann, Roy; Aletaha, Daniel; Kavanaugh, Arthur; van der Heijde, Désirée

2014-10-01

Investigator-initiated trials, some of which have been referred to as comparative effectiveness trials, pragmatic trials, or strategy trials, are sometimes considered to be of greater clinical importance than industry-driven trials, because they address important but unresolved clinical questions that differ from the questions asked in industry-driven trials. Regulatory authorities have provided methodological guidance for industry-driven trials for the approval of new treatments, but such guidance is less clear for investigator-initiated trials. The European League Against Rheumatism (EULAR) task force for the update of the recommendations for the management of rheumatoid arthritis has critically looked at the methodological quality and conduct of many investigator-initiated trials, and has identified a number of concerns. In this Viewpoint paper, we highlight commonly encountered issues that are discussed using examples of well-known investigator-initiated trials. These issues cover three themes: (1) design choice (superiority vs non-inferiority designs); (2) statistical power and (3) convenience reporting. Since we acknowledge the importance of investigator-initiated research, we also propose a shortlist of points-to-consider when designing, performing and reporting investigator-initiated trials. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Reversal of Sepsis-Like Features of Neutrophils by Interleukin-1 Blockade in Patients With Systemic-Onset Juvenile Idiopathic Arthritis.

PubMed

Ter Haar, Nienke M; Tak, Tamar; Mokry, Michal; Scholman, Rianne C; Meerding, Jenny M; de Jager, Wilco; Verwoerd, Anouk; Foell, Dirk; Vogl, Thomas; Roth, Johannes; Leliefeld, Pieter H C; van Loosdregt, Jorg; Koenderman, Leo; Vastert, Sebastiaan J; de Roock, Sytze

2018-06-01

Neutrophils are the most abundant innate immune cells in the blood, but little is known about their role in (acquired) chronic autoinflammatory diseases. This study was undertaken to investigate the role of neutrophils in systemic-onset juvenile idiopathic arthritis (JIA), a prototypical multifactorial autoinflammatory disease that is characterized by arthritis and severe systemic inflammation. Fifty patients with systemic-onset JIA who were receiving treatment with recombinant interleukin-1 receptor antagonist (rIL-1Ra; anakinra) were analyzed at disease onset and during remission. RNA sequencing was performed on fluorescence-activated cell-sorted neutrophils from 3 patients with active systemic-onset JIA and 3 healthy controls. Expression of activation markers, apoptosis, production of reactive oxygen species (ROS), and degranulation of secretory vesicles from neutrophils were assessed by flow cytometry in serum samples from 17 patients with systemic-onset JIA and 15 healthy controls. Neutrophil counts were markedly increased at disease onset, and this correlated with the levels of inflammatory mediators. The neutrophil counts normalized within days after the initiation of rIL-1Ra therapy. RNA-sequencing analysis revealed a substantial up-regulation of inflammatory processes in neutrophils from patients with active systemic-onset JIA, significantly overlapping with the transcriptome of sepsis. Correspondingly, neutrophils from patients with active systemic-onset JIA displayed a primed phenotype that was characterized by increased ROS production, CD62L shedding, and secretory vesicle degranulation, which was reversed by rIL-1Ra treatment in patients who had achieved clinical remission. Patients with a short disease duration had high neutrophil counts, more immature neutrophils, and a complete response to rIL-1Ra, whereas patients with symptoms for >1 month had normal neutrophil counts and an unsatisfactory response to rIL-1Ra. In vitro, rIL-1Ra antagonized the

Idiopathic ophthalmodynia and idiopathic rhinalgia: two topographic facial pain syndromes.

PubMed

Pareja, Juan A; Cuadrado, María L; Porta-Etessam, Jesús; Fernández-de-las-Peñas, César; Gili, Pablo; Caminero, Ana B; Cebrián, José L

2010-09-01

To describe 2 topographic facial pain conditions with the pain clearly localized in the eye (idiopathic ophthalmodynia) or in the nose (idiopathic rhinalgia), and to propose their distinction from persistent idiopathic facial pain. Persistent idiopathic facial pain, burning mouth syndrome, atypical odontalgia, and facial arthromyalgia are idiopathic facial pain syndromes that have been separated according to topographical criteria. Still, some other facial pain syndromes might have been veiled under the broad term of persistent idiopathic facial pain. Through a 10-year period we have studied all patients referred to our neurological clinic because of facial pain of unknown etiology that might deviate from all well-characterized facial pain syndromes. In a group of patients we have identified 2 consistent clinical pictures with pain precisely located either in the eye (n=11) or in the nose (n=7). Clinical features resembled those of other localized idiopathic facial syndromes, the key differences relying on the topographic distribution of the pain. Both idiopathic ophthalmodynia and idiopathic rhinalgia seem specific pain syndromes with a distinctive location, and may deserve a nosologic status just as other focal pain syndromes of the face. Whether all such focal syndromes are topographic variants of persistent idiopathic facial pain or independent disorders remains a controversial issue.

Anti-type II collagen antibodies, anti-CCP, IgA RF and IgM RF are associated with joint damage, assessed eight years after onset of juvenile idiopathic arthritis (JIA)

PubMed Central

2014-01-01

Background Early appearance of antibodies specific for native human type II collagen (anti-CII) characterizes an early inflammatory and destructive phenotype in adults with rheumatoid arthritis (RA). The objective of this study was to investigate the occurrence of anti-CII, IgM RF, IgA RF and anti-CCP in serum samples obtained early after diagnosis, and to relate the occurrence of autoantibodies to outcome after eight years of disease in children with juvenile idiopathic arthritis (JIA). Methods The Nordic JIA database prospectively included JIA patients followed for eight years with data on remission and joint damage. From this database, serum samples collected from 192 patients, at a median of four months after disease onset, were analysed for IgG anti-CII, IgM RF, IgA RF and IgG anti-CCP. Joint damage was assessed based on Juvenile Arthritis Damage Index for Articular damage (JADI-A), a validated clinical instrument for joint damage. Results Elevated serum levels of anti-CII occurred in 3.1%, IgM RF in 3.6%, IgA RF in 3.1% and anti-CCP in 2.6% of the patients. Occurrence of RF and anti-CCP did to some extent overlap, but rarely with anti-CII. The polyarticular and oligoarticular extended categories were overrepresented in patients with two or more autoantibodies. Anti-CII occurred in younger children, usually without overlap with the other autoantibodies and was associated with high levels of C-reactive protein (CRP) early in the disease course. All four autoantibodies were significantly associated with joint damage, but not with active disease at the eight-year follow up. Conclusions Anti-CII, anti-CCP, IgA RF and IgM RF detected early in the disease course predicted joint damage when assessed after eight years of disease. The role of anti-CII in JIA should be further studied. PMID:24944545

Botulinum toxin, a new treatment modality for chronic idiopathic constipation in children: long-term follow-up of a double-blind randomized trial.

PubMed

Keshtgar, Alireza S; Ward, Harry C; Sanei, Ahmad; Clayden, Graham S

2007-04-01

Myectomy of the internal anal sphincter (IAS) has been performed on some children after failure of medical treatment to treat idiopathic constipation. The aim of this study was to compare botulinum toxin injection with myectomy of the IAS in the treatment of chronic idiopathic constipation and soiling in children. This was a double-blind randomized trial. Patients between 4 and 16 years old were included in the study if they had failed to respond to laxative treatment and anal dilatation for chronic idiopathic constipation. All study patients had anorectal manometry and anal endosonography under ketamine anesthesia. Outcome was measured using a validated symptom severity (SS) scoring system, with scores ranging from 0 to 65. Of 42 children, 21 were randomized to the botulinum group and 21 were randomized to the myectomy group. At the 3-month follow-up, the median preoperative SS score improved from 34 (range = 19-47) to 20 (range = 2-43) in the botulinum group (P < .001) and from 31 (range = 18-49) to 19 (range = 3-47) in the myectomy group (P < .002). At the 12-month follow-up, the scores were 19 (range = 0-45) and 14.5 (range = 0-41) for the botulinum group and the myectomy group, respectively (P < .0001). There was no complication in both groups. Botulinum toxin is equally effective as and less invasive than myectomy of the IAS for chronic idiopathic constipation and fecal incontinence in children.

Comparison of rheumatoid arthritis clinical trial outcome measures: a simulation study.

PubMed

Anderson, Jennifer J; Bolognese, James A; Felson, David T

2003-11-01

Isolated studies have suggested that continuous measures of response may be better than predefined, dichotomous definitions (e.g., the American College of Rheumatology 20% improvement criteria [ACR20]) for discriminating between rheumatoid arthritis (RA) treatments. Our goal was to determine the statistical power of predefined dichotomous outcome measures (termed "a priori"), compared with that of continuous measures derived from trial data in which there was no predefined response threshold (termed "data driven"), and to evaluate the sensitivity to change of these measures in the context of different treatments and early versus later-stage disease. In order to generalize beyond results from a single trial, we performed simulation studies. We obtained summary data from trials comparing disease-modifying antirheumatic drugs (DMARDs) and from comparative coxib-placebo trials to test the power of 2 a priori outcomes, the ACR20 and improvement of the Disease Activity Score (DDAS), as well as 2 data-driven outcomes. We studied patients with early RA and those with later-stage RA (duration of <4 years and 4-9 years, respectively). We performed simulation studies, using the interrelationship of ACR core set measures in the trials to generate multiple trial data sets consistent with the original data. The data-driven outcomes had greater power than did the a priori measures. The DMARD comparison was more powerful in early disease than in later-stage disease (the sample sizes needed to achieve 80% power for the most powerful test were 64 for early disease versus 100 for later disease), but the coxib-versus-placebo comparison was less powerful in early disease than in later disease (the sample sizes needed to achieve 80% power were 200 and 100, respectively). When the effects of treatment on core set items were small and/or inconsistent, power was reduced, particularly for a less broadly based outcome (e.g., DDAS) compared with the ACR20. The simulation studies demonstrate

Self-limiting arthritis among patients fulfilling the 2010 ACR/EULAR classification criteria for rheumatoid arthritis in a very early arthritis cohort.

PubMed

Norli, Ellen Sauar; Brinkmann, Gina H; Kvien, Tore K; Bjørneboe, Olav; Haugen, Anne J; Nygaard, Halvor; Thunem, Cathrine; Lie, Elisabeth; Mjaavatten, Maria D

2016-12-01

To study occurrence of and factors associated with self-limiting arthritis among patients fulfilling the 2010 ACR/EULAR classification criteria for rheumatoid arthritis (RA) (2010 RA criteria) in patients with ≤16 weeks׳ duration of joint swelling. We applied the 2010 RA criteria in 1118 patients included in a 2-year longitudinal cohort. In all, 256 patients fulfilled the 2010 RA criteria at baseline; outcome was defined as either "self-limiting arthritis" (no DMARD use during follow-up, no swollen joints at last assessment, and no final clinical diagnosis of RA) or "persistent disease." The associations between baseline characteristics, including the components of the 2010 RA criteria score, and outcomes were studied. In total, 36 of 256 patients (14.1%) classified as having RA had self-limiting arthritis. These patients differed from patients with persistent disease according to ACPA positivity (11.1% vs. 65.0%, p < 0.001), duration of joint swelling (median = 47.5 vs. 66.0 days, p = 0.002), 2010 RA criteria points (median = 6.0 vs. 7.0, p < 0.001), and ever smoking (52.8% vs. 74.5%, p = 0.01). Having no serology points and no duration points were independent predictors of self-limiting arthritis. The rate of self-limiting arthritis was 2.7% vs. 29.4% among ACPA positive vs. ACPA negative patients (p < 0.001), and 32.5% when duration of joint swelling was <4 weeks vs. 10.6% with longer duration (p < 0.001). Negative ACPA status, short duration of joint swelling and being a never smoker were factors associated with self-limiting arthritis in early arthritis patients classified as having RA at presentation. Our findings contribute to identify patients who potentially do not need DMARDs and who should not be included in early RA clinical drug trials. Copyright © 2016 Elsevier Inc. All rights reserved.

Transitional care in clinical networks for young people with juvenile idiopathic arthritis: current situation and challenges.

PubMed

Cruikshank, Mary; Foster, Helen E; Stewart, Jane; Davidson, Joyce E; Rapley, Tim

2016-04-01

Clinical networks for paediatric and adolescent rheumatology are evolving, and their effect and role in the transition process between paediatric and adult services are unknown. We therefore explored the experiences of those involved to try and understand this further. Health professionals, young people with juvenile idiopathic arthritis and their families were recruited via five national health service paediatric and adolescent rheumatology specialist centres and networks across the UK. Seventy participants took part in focus groups and one-to-one interviews. Data was analysed using coding, memoing and mapping techniques to identify features of transitional services across the sector. Variation and inequities in transitional care exist. Although transition services in networks are evolving, development has lagged behind other areas with network establishment focusing more on access to paediatric rheumatology multidisciplinary teams. Challenges include workforce shortfalls, differences in service priorities, standards and healthcare infrastructures, and managing the legacy of historic encounters. Providing equitable high-quality clinically effective services for transition across the UK has a long way to go. There is a call from within the sector for more protected time, staff and resources to develop transition roles and services, as well as streamlining of local referral pathways between paediatric and adult healthcare services. In addition, there is a need to support professionals in developing their understanding of transitional care in clinical networks, particularly around service design, organisational change and the interpersonal skills required for collaborative working. Key messages • Transitional care in clinical networks requires collaborative working and an effective interface with paediatric and adult rheumatology.• Professional centrism and historic encounters may affect collaborative relationships within clinical networks.• Education

Ocular morbidities of juvenile idiopathic arthritis-associated uveitis in adulthood: results from a tertiary center study.

PubMed

Oray, Merih; Khachatryan, Naira; Ebrahimiadib, Nazanin; Abu Samra, Khawla; Lee, Stacey; Foster, C Stephen

2016-09-01

To describe the clinical and visual outcomes of juvenile idiopathic arthritis (JIA)-associated uveitis in adults and to examine risk factors for ongoing inflammation in adulthood. Medical records were reviewed for patients with JIA-associated uveitis who were >16 years old at the final visit (the last visit prior to data collection). In total, 135 eyes of 77 patients (70 female, 7 male) were included. The mean age of patients at the final visit was 29.72 ± 11.27 years. The number of eyes with visual acuity of ≤20/50 and ≤20/200 at the final visit was 37 (28 %) and 20 (15 %), respectively; at least one ocular complication was present in 72 % of eyes. Band keratopathy was the most frequent complication (42 %), followed by cataract (25 %), posterior synechiae (22 %), maculopathy (22 %), ocular hypertension (13 %), and hypotony (5 %). At the final visit, patients who were >16 years of age at presentation to the Massachusetts Eye Research and Surgery Institution had more ocular complications and a greater degree of vision loss than patients who were ≤16 years of age. Ongoing inflammation at the final visit was noted in 40 patients (52 %). The presence of posterior synechiae, hypotony, cataract at presentation, and a history of cataract surgery prior to presentation were predictive of ongoing inflammation in adulthood in univariate analysis. The presence of hypotony and posterior synechiae at the initial visit were predictive factors in multivariate analysis. JIA-associated uveitis may be associated with ongoing inflammation, ocular complications, and severe visual impairment in adulthood. The presence of posterior synechiae and hypotony at the initial visit is predictive of ongoing inflammation.

Protective role of HLA-DRB1*11 against juvenile idiopathic arthritis living in North Eastern Iran.

PubMed

Rezaieyazdi, Zahra; Kochakzadeh, Morteza; Hatef, Mohammad Reza; Esmaily, Habibollah; Malek, Abdolreza; Valizadeh, Narges; Tabaei, Samira; Rafatpanah, Houshang

2018-06-01

Juvenile idiopathic arthritis (JIA) is one of the most common chronic rheumatic diseases in children. The complex nature of this immune-mediated disease owes itself to several predisposing genes and environmental factors affecting its pathogenesis. Conducted in Iran, this study was originally intended to investigate every possible association between HLA DRB1 alleles and a susceptibility to JIA. In this case-control study, 45 patients with a definite diagnosis of JIA based on International League against Rheumatism (ILAR) criteria were compared against 46 healthy controls. DNA samples taken from both groups were analyzed using PCR-sequence specific primers (PCR-SSP) method. Data analysis including parametric and nonparametric test and multivariate analysis was undertaken using the SPSS 11.5 software. A P-value< 0.05 was regarded as statistically significant. Mean ages in case group and healthy controls were 14.64±6.21 and 13.73±6.39, respectively with no significant difference between the two groups ( P =0.515). Sex difference between JIA group and healthy controls was also not significant ( P =0.068). The frequency of HLA-DRB1*01 was found the most frequent HLA-RB1 in our patients (33.3%). No significant statistical correlation between various HLA-DRB1 alleles and clinical subtypes of the disease could be established from the data. HLA-DRB1*11 was shown to raise protection to JIA ( P =0.035, OR=2.755, 95% CI=0.963-8.055) in northeastern Iran. In addition, we found that HLA-RB1*09 is nominally associated with an increased risk of JIA ( P =0.56, OR=2, 05, 95% CI=0.18-23.63). HLA-DRB1*11 was shown to raise protection to JIA in northeastern Iran. The disparity of findings in other ethnicities prompts further investigations with larger sample sizes.

Bee venom acupuncture for rheumatoid arthritis: a systematic review of randomised clinical trials.

PubMed

Lee, Ju Ah; Son, Mi Ju; Choi, Jiae; Jun, Ji Hee; Kim, Jong-In; Lee, Myeong Soo

2014-11-07

To assess the clinical evidence for bee venom acupuncture (BVA) for rheumatoid arthritis (RA). Systematic review of randomised controlled trials (RCTs). We searched 14 databases up to March 2014 without a language restriction. Patients with RA. BVA involved injecting purified, diluted BV into acupoints. We included trials on BVA used alone or in combination with a conventional therapy versus the conventional therapy alone. Morning stiffness, pain and joint swelling Erythrocyte sedimentation rate (ESR), C reactive protein (CRP), rheumatoid factor, the number of joints affected by RA and adverse effects likely related to RA. A total of 304 potentially relevant studies were identified; only one RCT met our inclusion criteria. Compared with placebo, BVA may more effectively improve joint pain, swollen joint counts, tender joint counts, ESR and CRP but was not shown to improve morning stiffness. There is low-quality evidence, based on one trial, that BVA can significantly reduce pain, morning stiffness, tender joint counts, swollen joint counts and improve the quality of life of patients with RA compared with placebo (normal saline injection) control. However, the number of trials, their quality and the total sample size were too low to draw firm conclusions. PROSPERO 2013: CRD42013005853. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Circulating complexes between tumour necrosis factor-alpha and etanercept predict long-term efficacy of etanercept in juvenile idiopathic arthritis.

PubMed

Kahn, Robin; Berthold, Elisabet; Gullstrand, Birgitta; Schmidt, Tobias; Kahn, Fredrik; Geborek, Pierre; Saxne, Tore; Bengtsson, Anders A; Månsson, Bengt

2016-04-01

The relationship between tumour necrosis factor-alpha (TNF-α) and drug survival had not been studied in juvenile idiopathic arthritis (JIA), and there were no laboratory tests to predict the long-term efficacy of biological drugs for JIA. We studied whether serum levels of TNF-α, free or bound to etanercept, could predict long-term efficacy of etanercept in children with JIA. We included 41 biologic-naïve patients with JIA who started treatment with etanercept at Skåne University Hospital between 1999 and 2010. Serum taken at the start of treatment and at the six-week follow-up were analysed for TNF-α and the long-term efficacy of etanercept was assessed using the drug survival time. Levels of TNF-α increased significantly at the six-week follow-up, and this was almost exclusively comprised of TNF-α in complex with etanercept. The increase in TNF-α showed a dose-dependent correlation to long-term drug survival (p < 0.01). Increasing levels of circulating TNF-α at treatment initiation predicted long-term efficacy of etanercept in children with JIA, which may have been due to different pathophysiological mechanisms of inflammation. Our result may provide a helpful clinical tool, as high levels of circulating TNF-α/etanercept complexes could be used as a marker for the long-term efficacy of etanercept. ©2015 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.

Visual Field Outcomes for the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT).

PubMed

Wall, Michael; Johnson, Chris A; Cello, Kimberly E; Zamba, K D; McDermott, Michael P; Keltner, John L

2016-03-01

The Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) showed that acetazolamide provided a modest, significant improvement in mean deviation (MD). Here, we further analyze visual field changes over the 6-month study period. Of 165 subjects with mild visual loss in the IIHTT, 125 had perimetry at baseline and 6 months. We evaluated pointwise linear regression of visual sensitivity versus time to classify test locations in the worst MD (study) eye as improving or not; pointwise changes from baseline to month 6 in decibels; and clinical consensus of change from baseline to 6 months. The average study eye had 36 of 52 test locations with improving sensitivity over 6 months using pointwise linear regression, but differences between the acetazolamide and placebo groups were not significant. Pointwise results mostly improved in both treatment groups with the magnitude of the mean change within groups greatest and statistically significant around the blind spot and the nasal area, especially in the acetazolamide group. The consensus classification of visual field change from baseline to 6 months in the study eye yielded percentages (acetazolamide, placebo) of 7.2% and 17.5% worse, 35.1% and 31.7% with no change, and 56.1% and 50.8% improved; group differences were not statistically significant. In the IIHTT, compared to the placebo group, the acetazolamide group had a significant pointwise improvement in visual field function, particularly in the nasal and pericecal areas; the latter is likely due to reduction in blind spot size related to improvement in papilledema. (ClinicalTrials.gov number, NCT01003639.).

The Effect of Positive Family History of Autoimmunity in Juvenile Idiopathic Arthritis Characteristics; a Case Control Study

PubMed Central

Khani, Mehdi; Ziaee, Vahid; Moradinejad, Mohamad-Hassan; Parvaneh, Nima

2013-01-01

Objective To compare Juvenile Idiopathic Arthritis (JIA) patients with and without family history of autoimmune disease with respect to clinical features and laboratory data. Methods Sixteen JIA patients with family history of autoimmune disease were identified during study, 32 patients were chosen for comparative group from referred patients to the rheumatology clinic according to the date of referral. Two groups were compared with respect to age of onset, sex, subtype, disease activity, duration of active disease and laboratory variables. Findings The age of onset was significantly lower in JIA patients with family history of autoimmunity (4.7 years vs. 7.0 years; P=0.02), polyarthicular subtype was more frequent in patients with positive family history (50% vs.25%; P=0.04) most of JIA patients with positive family history were in the active phase at the time of study (64% vs 25%; P=0.02) and had a longer duration of active disease (21.0 months vs 12.3 months; P=0.04). Patients with positive family history had more positive ANA (43.5%% vs 12.5%; P=0.01) and also more positive ADA (75% vs 20.8%; P=0.002). Two groups were similar according to sex, and other laboratory variables. Conclusion JIA patients with family history of autoimmune disease seem to have a more severe disease than patients without such family history, they are younger at the onset, and have mostly poyarthicular subtype. They also have more ANA and ADA positivity. These findings are different from familial JIA case-control studies according to active disease duration, subtype, and ANA positivity. PMID:24800019

Social/economic costs and health-related quality of life in patients with juvenile idiopathic arthritis in Europe.

PubMed

Kuhlmann, A; Schmidt, T; Treskova, M; López-Bastida, J; Linertová, R; Oliva-Moreno, J; Serrano-Aguilar, P; Posada-de-la-Paz, M; Kanavos, P; Taruscio, D; Schieppati, A; Iskrov, G; Péntek, M; Delgado, C; von der Schulenburg, J M; Persson, U; Chevreul, K; Fattore, G

2016-04-01

The aim of this study was to determine the economic burden from a societal perspective and the health-related quality of life (HRQOL) of patients with juvenile idiopathic arthritis (JIA) in Europe. We conducted a cross-sectional study of patients with JIA from Germany, Italy, Spain, France, the United Kingdom, Bulgaria, and Sweden. Data on demographic characteristics, healthcare resource utilization, informal care, labor productivity losses, and HRQOL were collected from the questionnaires completed by patients or their caregivers. HRQOL was measured with the EuroQol 5-domain (EQ-5D-5L) questionnaire. A total of 162 patients (67 Germany, 34 Sweden, 33 Italy, 23 United Kingdom, 4 France, and 1 Bulgaria) completed the questionnaire. Excluding Bulgarian results, due to small sample size, country-specific annual health care costs ranged from €18,913 to €36,396 (reference year: 2012). Estimated direct healthcare costs ranged from €11,068 to €22,138; direct non-healthcare costs ranged from €7837 to €14,155 and labor productivity losses ranged from €0 to €8715. Costs are also shown to differ between children and adults. The mean EQ-5D index score for JIA patients was estimated at between 0.44 and 0.88, and the mean EQ-5D visual analogue scale score was estimated at between 62 and 79. JIA patients incur considerable societal costs and experience substantial deterioration in HRQOL in some countries. Compared with previous studies, our results show a remarkable increase in annual healthcare costs for JIA patients. Reasons for the increase are the inclusion of non-professional caregiver costs, a wider use of biologics, and longer hospital stays.

Limited value of cyclosporine A for the treatment of patients with uveitis associated with juvenile idiopathic arthritis.

PubMed

Tappeiner, C; Roesel, M; Heinz, C; Michels, H; Ganser, G; Heiligenhaus, A

2009-05-01

Juvenile idiopathic arthritis (JIA) is often associated with severe chronic anterior uveitis (CAU), and immunosuppressive therapy may be required. In this study, the value of cyclosporine A (CsA) as monotherapy or as combination therapy for treating uveitis was studied in a large cohort of JIA children. Multicentre retrospective study including 82 JIA children (girls n=60) suffering from unilateral or bilateral (n=55) CAU. The indication for CsA was active uveitis, although patients were on topical or systemic corticosteroids, MTX, or other immunosuppressive drugs. Inactivity of uveitis during the entire treatment period (mean 3.9 years) was obtained with CsA monotherapy in 6 of 25 (24%) patients, but more often when CsA was combined with the immunosuppressives (35/72 patients; 48.6%, P=0.037), or MTX (18/37 patients, 48.6%, P=0.065), which had already been given. With CsA (mean dosage 2.9 mg/kg), systemic immunosuppressive drugs and steroids could be reduced by >or=50% (n=19) or topical steroids reduced to

Bacillus coagulans: a viable adjunct therapy for relieving symptoms of rheumatoid arthritis according to a randomized, controlled trial.

PubMed

Mandel, David R; Eichas, Katy; Holmes, Judith

2010-01-12

Lactic acid-producing bacteria (LAB) probiotics demonstrate immunomodulating and anti-inflammatory effects and the ability to lessen the symptoms of arthritis in both animals and humans. This randomized, double-blind, placebo-controlled, parallel-design, clinical pilot trial was conducted to evaluate the effects of the LAB probiotic preparation, Bacillus coagulans GBI-30, 6086, on symptoms and measures of functional capacity in patients with rheumatoid arthritis (RA) in combination with pharmacological anti-arthritic medications. Forty-five adult men and women with symptoms of RA were randomly assigned to receive Bacillus coagulans GBI-30, 6086 or placebo once a day in a double-blind fashion for 60 days in addition to their standard anti-arthritic medications. Arthritis activity was evaluated by clinical examination, the American College of Rheumatology (ACR) criteria, the Stanford Health Assessment Questionnaire Disability Index (HAQ-DI), and laboratory tests for erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Subjects who received Bacillus coagulans GBI-30, 6086 experienced borderline statistically significant improvement in the Patient Pain Assessment score (P = .052) and statistically significant improvement in Pain Scale (P = .046) vs placebo. Compared with placebo, Bacillus coagulans GBI-30, 6086 treatment resulted in greater improvement in patient global assessment and self-assessed disability; reduction in CRP; as well as the ability to walk 2 miles, reach, and participate in daily activities. There were no treatment-related adverse events reported throughout this study. Results of this pilot study suggest that adjunctive treatment with Bacillus coagulans GBI-30, 6086 LAB probiotic appeared to be a safe and effective for patients suffering from RA. Because of the low study population size, larger trials are needed to verify these results. ACTRN12609000435280.

A Qualitative Study of Fitness Instructors' Experiences Leading an Exercise Program for Children with Juvenile Idiopathic Arthritis

ERIC Educational Resources Information Center

Hutzal, Carolyn E.; Wright, F. Virginia; Stephens, Samantha; Schneiderman-Walker, Jane; Feldman, Brian M.

2009-01-01

Children with arthritis face challenges when they try to increase their physical activity. The study's objective was to identify elements of a successful community-based exercise program for children with arthritis by investigating the perspectives of fitness instructors who led the program. This qualitative study used a phenomenological approach.…

Adding patient-reported outcomes to a multisite registry to quantify quality of life and experiences of disease and treatment for youth with juvenile idiopathic arthritis.

PubMed

Weitzman, Elissa R; Wisk, Lauren E; Salimian, Parissa K; Magane, Kara M; Dedeoglu, Fatma; Hersh, Aimee O; Kimura, Yukiko; Mandl, Kenneth D; Ringold, Sarah; Natter, Marc

2018-01-01

Children with Juvenile Idiopathic Arthritis (JIA) often have poor health-related quality of life (HRQOL) despite advances in treatment. Patient-centered research may shed light on how patient experiences of treatment and disease contribute to HRQOL, pinpointing directions for improving care and enhancing outcomes. Parent proxies of youth enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry shared patient-reported outcomes about their child's HRQOL and experiences of disease and treatment burden (pain interference, morning stiffness, history of medication side effects and methotrexate intolerance). Contributions of these measures to HRQOL were estimated using generalized estimating equations accounting for site and patient demographics. Patients ( N = 180) were 81.1% white non-Hispanic and 76.7% female. Mean age was 11.8 (SD = 3.6) years, mean disease duration was 7.7 years (SD = 3.5). Mean Total Pediatric Quality of Life was 76.7 (SD = 18.2). Mean pain interference score was 50.1 (SD = 11.1). Nearly one-in-five (17.8%) youth experienced >15 min of morning stiffness on a typical day, more than one quarter (26.7%) reported ≥1 serious medication side effect and among 90 methotrexate users, 42.2% met criteria for methotrexate intolerance. Measures of disease and treatment burden were independently negatively associated with HRQOL (all p -values <0.01). Negative associations among measures of treatment burden and HRQOL were attenuated after controlling for disease burden and clinical characteristics but remained significant. For youth with JIA, HRQOL is multidimensional, reflecting disease as well as treatment factors. Adverse treatment experiences undermine HRQOL even after accounting for disease symptoms and disease activity and should be assessed routinely to improve wellbeing.

Clinically inactive disease in a cohort of children with new-onset polyarticular juvenile idiopathic arthritis treated with early aggressive therapy: time to achievement, total duration, and predictors.

PubMed

Wallace, Carol A; Giannini, Edward H; Spalding, Steven J; Hashkes, Philip J; O'Neil, Kathleen M; Zeft, Andrew S; Szer, Ilona S; Ringold, Sarah; Brunner, Hermine I; Schanberg, Laura E; Sundel, Robert P; Milojevic, Diana S; Punaro, Marilynn G; Chira, Peter; Gottlieb, Beth S; Higgins, Gloria C; Ilowite, Norman T; Kimura, Yukiko; Johnson, Anne; Huang, Bin; Lovell, Daniel J

2014-06-01

To determine the elapsed time while receiving aggressive therapy to the first observation of clinically inactive disease (CID), total duration of CID and potential predictors of this response in a cohort of children with recent onset of polyarticular juvenile idiopathic arthritis (poly-JIA). Eighty-five children were randomized blindly to methotrexate (MTX), etanercept, and rapidly tapered prednisolone (MEP) or MTX monotherapy and assessed for CID over 1 year of treatment. Patients who failed to achieve intermediary endpoints were switched to open-label MEP treatment. Fifty-eight (68.2%) of the 85 patients achieved CID at 1 or more visits including 18 who received blinded MEP, 11 while receiving MTX monotherapy, and 29 while receiving open-label MEP. Patients starting on MEP achieved CID earlier and had more study days in CID compared to those starting MTX, but the differences were not significantly different. Patients given MEP (more aggressive therapy) earlier in the disease course were statistically more likely to have a higher proportion of followup visits in CID than those with longer disease course at baseline. Those who achieved American College of Rheumatology Pediatric 70 response at 4 months had a significantly greater proportion of followup visits in CID, compared to those who failed to achieve this improvement (p < 0.0001). Of the 32 patients who met criteria for CID and then lost CID status, only 3 fulfilled the definition of disease flare. Shorter disease duration prior to treatment, a robust response at 4 months, and more aggressive therapy result in a higher likelihood and longer duration of CID in patients with poly-JIA. The original trial from which data for this analysis were obtained is registered on www.clinicaltrials.gov NCT 00443430.

Review article: moving towards common therapeutic goals in Crohn's disease and rheumatoid arthritis.

PubMed

Allen, P B; Olivera, P; Emery, P; Moulin, D; Jouzeau, J-Y; Netter, P; Danese, S; Feagan, B; Sandborn, W J; Peyrin-Biroulet, L

2017-04-01

Crohn's disease (CD) and rheumatoid arthritis are chronic, progressive and disabling conditions that frequently lead to structural tissue damage. Based on strategies originally developed for rheumatoid arthritis, the treatment goal for CD has recently moved from exclusively controlling symptoms to both clinical remission and complete mucosal healing (deep remission), with the final aim of preventing bowel damage and disability. To review the similarities and differences in treatment goals between CD and rheumatoid arthritis. This review examined manuscripts from 1982 to 2016 that discussed and/or proposed therapeutic goals with their supportive evidence in CD and rheumatoid arthritis. Proposed therapeutic strategies to improve outcomes in both rheumatoid arthritis and CD include: (i) evaluation of musculoskeletal or organ damage and disability, (ii) tight control, (iii) treat-to-target, (iv) early intervention and (v) disease modification. In contrast to rheumatoid arthritis, there is a paucity of disease-modification trials in CD. Novel therapeutic strategies in CD based on tight control of objective signs of inflammation are expected to change disease course and patients' lives by halting progression or, ideally, preventing the occurrence of bowel damage. Most of these strategies require validation in prospective studies, whereas several disease-modification trials have addressed these issues in rheumatoid arthritis over the last decade. The recent approval of new drugs in CD such as vedolizumab and ustekinumab should facilitate initiation of disease-modification trials in CD in the near future. © 2017 John Wiley & Sons Ltd.

Synovial fluid proteomics in the pursuit of arthritis mediators: An evolving field of novel biomarker discovery.

PubMed

Mahendran, Shalini M; Oikonomopoulou, Katerina; Diamandis, Eleftherios P; Chandran, Vinod

Synovial fluid (SF) is a protein-rich fluid produced into the joint cavity by cells of the synovial membrane. Due to its direct contact with articular cartilage, surfaces of the bone, and the synoviocytes of the inner membrane, it provides a promising reflection of the biochemical state of the joint under varying physiological and pathophysiological conditions. This property of SF has been exploited within numerous studies in search of unique biomarkers of joint pathologies with the ultimate goal of developing minimally invasive clinical assays to detect and/or monitor disease states. Several proteomic methodologies have been employed to mine the SF proteome. From elementary immunoassays to high-throughput analyses using mass spectrometry-based techniques, each has demonstrated distinct advantages and disadvantages in the identification and quantification of SF proteins. This review will explore the role of SF in the elucidation of the arthritis proteome and the extent to which high-throughput techniques have facilitated the discovery and validation of protein biomarkers from osteoarthritis (OA), rheumatoid arthritis (RA), psoriatic arthritis (PsA), and juvenile idiopathic arthritis (JIA) patients.

Evidence based knee injections for the management of arthritis

PubMed Central

Cheng, Olivia T.; Souzdalnitski, Dmitri; Vrooman, Bruce; Cheng, Jianguo

2012-01-01

Objective Arthritis of the knee affects 46 million Americans. We aimed to determine the level of evidence of intraarticular knee injections in the management of arthritic knee pain. Methods We systematically searched PUBMED/MEDLINE and the Cochrane databases for articles published on knee injections and evaluated their level of evidence and recommendations according to established criteria. Results The evidence supports the use of intraarticular corticosteroid injections for rheumatoid arthritis (1A+ level), osteoarthritis (1A+ level), and juvenile idiopathic arthritis (2C+ level). Pain relief and functional improvement are significant for months up to one year after the injection. Triamcinolone hexacetonide offers an advantage over triamcinolone acetonide and should be the intraarticular steroid of choice (2B+ level). Intraarticular injection of hyaluronate may provide longer pain relief than steroid injection in osteoarthritis (2B+ level). It can also be effective for rheumatoid arthritis knee pain (1A+ level). However, it is only recommended for patients with significant surgical risk factors and for patients with mild radiographic disease in whom conservative treatment has failed (2B± level). Botulinum toxin Type A injection is effective in reducing arthritic knee pain (2B+ level) and so is tropisetron (2B+ level) and tanezumab (2B+ level). The new agents, such as rAAV2-TNFR:Fc, SB-210396/CE 9.1, and various radioisotopes have provided various degrees of success, but their long-term safety and efficacy remains to be determined. Conclusions We conclude that strong evidence supports the use of intraarticular knee injection as a valuable intervention in the continuum of management of arthritis between conservative treatment and knee surgeries. PMID:22621287

Yoga for Arthritis: A Scoping Review

PubMed Central

Haaz, Steffany; Bartlett, Susan J.

2010-01-01

Synopsis The aim of this article was to systematically review the existing literature on the use of yoga for persons with arthritis. We included peer-reviewed research from clinical trials (published from 1980-2010) that used yoga as an intervention for arthritis patients and reported quantitative findings. Eleven studies were identified, including four RCTs and four NRCTs. All trials were small and control groups varied. No adverse events were reported and attrition was comparable or better than typical for exercise interventions. Evidence was strongest for reduction in disease symptoms (tender/swollen joints, pain) and disability, as well as improved self-efficacy and mental health. Interventions, research methods and disease diagnoses were heterogeneous. Larger, rigorous RCTs are necessary to more effectively quantify the effects of yoga for arthritic populations PMID:21220084

Prevalence of Arthritis in Africa: A Systematic Review and Meta-Analysis

PubMed Central

Usenbo, Anthony; Kramer, Veronika; Young, Taryn; Musekiwa, Alfred

2015-01-01

Objective In this systematic review, we estimate the prevalence of six types of arthritis in Africa; namely rheumatoid arthritis, osteoarthritis, juvenile arthritis, psoriatic arthritis, gout, and ankylosing spondylitis. Methods We comprehensively searched literature on 31 August 2014 in MEDLINE, EMBASE, Web of Science and the Cochrane Library to identify eligible studies from 1975 up to 31 July 2014. Two review authors independently selected studies, extracted data, and appraised studies. We carried out random effects meta-analysis of prevalence of arthritis and assessed heterogeneity through subgroup analyses. We performed separate analyses for population- and hospital-based studies, as well as rural and urban settings. Main Findings We included 27 cross-sectional studies (20 population-based and 7 hospital-based) from Africa reporting on the prevalence of arthritis. The majority of the studies were from South Africa (44.4%, 12/27). Rheumatoid arthritis in urban settings ranged from 0.1% in Algeria, 0.6% in the DRC, to a meta-analysis overall prevalence of 2.5% in South Africa, and in rural settings ranged from a meta-analysis overall prevalence of 0.07% in South Africa, 0.3% in Egypt, to 0.4% in Lesotho. Osteoarthritis was the most prevalent form of arthritis and in urban settings it was 55.1% in South Africa and in rural settings, all in South Africa, ranged from 29.5%, 29.7%, up to 82.7% among adults aged over 65 years. Other results include highest prevalence of 33.1% for knee osteoarthritis in rural South Africa, 0.1% for ankylosing spondylitis in rural South Africa, 4.4% for psoriatic arthritis in urban South Africa, 0.7% for gout in urban South Africa, and 0.3% for juvenile idiopathic arthritis in urban Egypt. A third of the included studies had a low risk of bias (33.3%, 9/27), 40.8% (11/27) moderate risk, and 25.9% (7/27) had a high risk of bias. Conclusions In this systematic review, we have identified the paucity of latest prevalence data on arthritis

Prevalence of Arthritis in Africa: A Systematic Review and Meta-Analysis.

PubMed

Usenbo, Anthony; Kramer, Veronika; Young, Taryn; Musekiwa, Alfred

2015-01-01

In this systematic review, we estimate the prevalence of six types of arthritis in Africa; namely rheumatoid arthritis, osteoarthritis, juvenile arthritis, psoriatic arthritis, gout, and ankylosing spondylitis. We comprehensively searched literature on 31 August 2014 in MEDLINE, EMBASE, Web of Science and the Cochrane Library to identify eligible studies from 1975 up to 31 July 2014. Two review authors independently selected studies, extracted data, and appraised studies. We carried out random effects meta-analysis of prevalence of arthritis and assessed heterogeneity through subgroup analyses. We performed separate analyses for population- and hospital-based studies, as well as rural and urban settings. We included 27 cross-sectional studies (20 population-based and 7 hospital-based) from Africa reporting on the prevalence of arthritis. The majority of the studies were from South Africa (44.4%, 12/27). Rheumatoid arthritis in urban settings ranged from 0.1% in Algeria, 0.6% in the DRC, to a meta-analysis overall prevalence of 2.5% in South Africa, and in rural settings ranged from a meta-analysis overall prevalence of 0.07% in South Africa, 0.3% in Egypt, to 0.4% in Lesotho. Osteoarthritis was the most prevalent form of arthritis and in urban settings it was 55.1% in South Africa and in rural settings, all in South Africa, ranged from 29.5%, 29.7%, up to 82.7% among adults aged over 65 years. Other results include highest prevalence of 33.1% for knee osteoarthritis in rural South Africa, 0.1% for ankylosing spondylitis in rural South Africa, 4.4% for psoriatic arthritis in urban South Africa, 0.7% for gout in urban South Africa, and 0.3% for juvenile idiopathic arthritis in urban Egypt. A third of the included studies had a low risk of bias (33.3%, 9/27), 40.8% (11/27) moderate risk, and 25.9% (7/27) had a high risk of bias. In this systematic review, we have identified the paucity of latest prevalence data on arthritis in Africa. More studies are needed to

Pirfenidone for idiopathic pulmonary fibrosis: analysis of pooled data from three multinational phase 3 trials.

PubMed

Noble, Paul W; Albera, Carlo; Bradford, Williamson Z; Costabel, Ulrich; du Bois, Roland M; Fagan, Elizabeth A; Fishman, Robert S; Glaspole, Ian; Glassberg, Marilyn K; Lancaster, Lisa; Lederer, David J; Leff, Jonathan A; Nathan, Steven D; Pereira, Carlos A; Swigris, Jeffrey J; Valeyre, Dominique; King, Talmadge E

2016-01-01

Pirfenidone is an antifibrotic agent that has been evaluated in three multinational phase 3 trials in patients with idiopathic pulmonary fibrosis (IPF). We analysed pooled data from the multinational trials to obtain the most precise estimates of the magnitude of treatment effect on measures of disease progression.All patients randomised to pirfenidone 2403 mg·day(-1) or placebo in the CAPACITY or ASCEND studies were included in the analysis. Pooled analyses of outcomes at 1 year were based on the pre-specified end-points and analytic methods described in the ASCEND study protocol.A total of 1247 patients were included in the analysis. At 1 year, pirfenidone reduced the proportion of patients with a ≥10% decline in per cent predicted forced vital capacity or death by 43.8% (95% CI 29.3-55.4%) and increased the proportion of patients with no decline by 59.3% (95% CI 29.0-96.8%). A treatment benefit was also observed for progression-free survival, 6-min walk distance and dyspnoea. Gastrointestinal and skin-related adverse events were more common in the pirfenidone group, but rarely led to discontinuation.Analysis of data from three phase 3 trials demonstrated that treatment with pirfenidone for 1 year resulted in clinically meaningful reductions in disease progression in patients with IPF. Copyright ©ERS 2016.

Pirfenidone for idiopathic pulmonary fibrosis: analysis of pooled data from three multinational phase 3 trials

PubMed Central

Albera, Carlo; Bradford, Williamson Z.; Costabel, Ulrich; du Bois, Roland M.; Fagan, Elizabeth A.; Fishman, Robert S.; Glaspole, Ian; Glassberg, Marilyn K.; Lancaster, Lisa; Lederer, David J.; Leff, Jonathan A.; Nathan, Steven D.; Pereira, Carlos A.; Swigris, Jeffrey J.; Valeyre, Dominique; King, Talmadge E.

2016-01-01

Pirfenidone is an antifibrotic agent that has been evaluated in three multinational phase 3 trials in patients with idiopathic pulmonary fibrosis (IPF). We analysed pooled data from the multinational trials to obtain the most precise estimates of the magnitude of treatment effect on measures of disease progression. All patients randomised to pirfenidone 2403 mg·day−1 or placebo in the CAPACITY or ASCEND studies were included in the analysis. Pooled analyses of outcomes at 1 year were based on the pre-specified end-points and analytic methods described in the ASCEND study protocol. A total of 1247 patients were included in the analysis. At 1 year, pirfenidone reduced the proportion of patients with a ≥10% decline in per cent predicted forced vital capacity or death by 43.8% (95% CI 29.3–55.4%) and increased the proportion of patients with no decline by 59.3% (95% CI 29.0–96.8%). A treatment benefit was also observed for progression-free survival, 6-min walk distance and dyspnoea. Gastrointestinal and skin-related adverse events were more common in the pirfenidone group, but rarely led to discontinuation. Analysis of data from three phase 3 trials demonstrated that treatment with pirfenidone for 1 year resulted in clinically meaningful reductions in disease progression in patients with IPF. PMID:26647432

Using short-term evidence to predict six-month outcomes in clinical trials of signs and symptoms in rheumatoid arthritis.

PubMed

Nixon, Richard M; Bansback, Nick; Stevens, John W; Brennan, Alan; Madan, Jason

2009-01-01

A model is presented to generate a distribution for the probability of an ACR response at six months for a new treatment for rheumatoid arthritis given evidence from a one- or three-month clinical trial. The model is based on published evidence from 11 randomized controlled trials on existing treatments. A hierarchical logistic regression model is used to find the relationship between the proportion of patients achieving ACR20 and ACR50 at one and three months and the proportion at six months. The model is assessed by Bayesian predictive P-values that demonstrate that the model fits the data well. The model can be used to predict the number of patients with an ACR response for proposed six-month clinical trials given data from clinical trials of one or three months duration. Copyright 2008 John Wiley & Sons, Ltd.

Internet-Based Implementation of Non-Pharmacological Interventions of the "People Getting a Grip on Arthritis" Educational Program: An International Online Knowledge Translation Randomized Controlled Trial Design Protocol

PubMed Central

Thomas, Roanne; De Angelis, Gino

2015-01-01

Background Rheumatoid arthritis (RA) affects 2.1% of the Australian population (1.5% males; 2.6% females), with the highest prevalence from ages 55 to over 75 years (4.4-6.1%). In Canada, RA affects approximately 0.9% of adults, and within 30 years that is expected to increase to 1.3%. With an aging population and a greater number of individuals with modifiable risk factors for chronic diseases, such as arthritis, there is an urgent need for co-care management of arthritic conditions. The increasing trend and present shifts in the health services and policy sectors suggest that digital information delivery is becoming more prominent. Therefore, it is necessary to further investigate the use of online resources for RA information delivery. Objective The objective is to examine the effect of implementing an online program provided to patients with RA, the People Getting a Grip on Arthritis for RA (PGrip-RA) program, using information communication technologies (ie, Facebook and emails) in combination with arthritis health care professional support and electronic educational pamphlets. We believe this can serve as a useful and economical method of knowledge translation (KT). Methods This KT randomized controlled trial will use a prospective randomized open-label blinded-endpoint design to compare four different intervention approaches of the PGrip-RA program to a control group receiving general electronic educational pamphlets self-management in RA via email. Depending on group allocation, links to the Arthritis Society PGrip-RA material will be provided either through Facebook or by email. One group will receive feedback online from trained health care professionals. The intervention period is 6 weeks. Participants will have access to the Internet-based material after the completion of the baseline questionnaires until the final follow-up questionnaire at 6 months. We will invite 396 patients from Canadian and Australian Arthritis Consumers’ Associations to

Consensus statement on blocking the effects of interleukin-6 and in particular by interleukin-6 receptor inhibition in rheumatoid arthritis and other inflammatory conditions

PubMed Central

Smolen, Josef S; Schoels, Monika M; Nishimoto, Norihiro; Breedveld, Ferdinand C; Burmester, Gerd R; Dougados, Maxime; Emery, Paul; Ferraccioli, Gianfranco; Gabay, Cem; Gibofsky, Allan; Gomez-Reino, Juan Jesus; Jones, Graeme; Kvien, Tore K; Murakami, Miho; Betteridge, Neil; Bingham, Clifton O; Bykerk, Vivian; Choy, Ernest H; Combe, Bernard; Cutolo, Maurizio; Graninger, Winfried; Lanas, Angel; Martin-Mola, Emilio; Montecucco, Carlomaurizio; Ostergaard, Mikkel; Pavelka, Karel; Rubbert-Roth, Andrea; Sattar, Naveed; Scholte-Voshaar, Marieke; Tanaka, Yoshiya; Trauner, Michael; Valentini, Gabriele; Winthrop, Kevin L; de Wit, Maarten; van der Heijde, Désirée

2013-01-01

Background Since approval of tocilizumab (TCZ) for treatment of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA), interleukin 6 (IL-6) pathway inhibition was evaluated in trials of TCZ and other agents targeting the IL-6 receptor and ligand in various RA populations and other inflammatory diseases. This consensus document informs on interference with the IL-6 pathway based on evidence and expert opinion. Methods Preparation of this document involved international experts in RA treatment and RA patients. A systematic literature search was performed that focused on TCZ and other IL6-pathway inhibitors in RA and other diseases. Subsequently, incorporating available published evidence and expert opinion, the steering committee and a broader expert committee (both including RA patients) formulated the current consensus statement. Results The consensus statement covers use of TCZ as combination- or monotherapy in various RA populations and includes clinical, functional and structural aspects. The statement also addresses the second approved indication in Europe JIA and non-approved indications. Also early phase trials involving additional agents that target the IL-6 receptor or IL-6 were evaluated. Safety concerns, including haematological, hepatic and metabolic issues as well as infections, are addressed likewise. Conclusions The consensus statement identifies points to consider when using TCZ, regarding indications, contraindications, screening, dose, comedication, response evaluation and safety. The document is aimed at supporting clinicians and informing patients, administrators and payers on opportunities and limitations of IL-6 pathway inhibition. PMID:23172750

[Progress on rheumatoid arthritis in elderly].

PubMed

Wang, Xin; Zhao, Qin; Deng, Zhao-da; Wang, Xiao-Yuan; Zhang, Si-Gong; Shen, Hai-Li

2017-06-25

During choosing non-steroidal anti-inflammatory drugs(NSAIDs), risk factors should be evaluated in elder patients with rheumatoid arthritis. The present study focused on biological therapies, and elderly patients should be more concerned about the risk of infection when used it. Traditional Chinese medicine has advantages of obvious curative effect, especially for tripterygium wilfordii, large clinical trial on western and Chinese medical accurate drug strategies for old patients with rheumatoid arthritis. Old patients are easier to suffer from cardiac diseases and interstitial lung disease, rheumatoid arthritis could be controlled along with the treatment for coexistent disease. The incidence of rheumatoid arthritis in old patients is the same with other RA, and need to treat to target based on the aim of relieve pain and reduce activity of diseases, while the clinical charteristic and treatment target in elder patients with rheumatoid arthritis were not similar with other aged patient, so treatment standard target would vary with aging. Resent clinical studies excluded old patients, lead to lack of evidence-based medicine data. Clinical study for elder patients with rheumatoid arthritis are energetically carrying out, and could provide base and guide for clinical treatment. Copyright© 2017 by the China Journal of Orthopaedics and Traumatology Press.

A Randomized, Controlled Trial of Emotional Disclosure in Rheumatoid Arthritis: Can Clinician Assistance Enhance the Effects?

PubMed Central

Keefe, Francis J.; Anderson, Timothy; Lumley, Mark; Caldwell, David; Stainbrook, David; Mckee, Daphne; Waters, Sandra J.; Connelly, Mark; Affleck, Glenn; Pope, Mary Susan; Weiss, Marianne; Riordan, Paul A.; Uhlin, Brian D.

2008-01-01

Emotional disclosure by writing or talking about stressful life experiences improves health status in non-clinical populations, but its success in clinical populations, particularly rheumatoid arthritis (RA), has been mixed. In this randomized, controlled trial, we attempted to increase the efficacy of emotional disclosure by having a trained clinician help patients emotionally disclose and process stressful experiences. We randomized 98 adults with RA to one of four conditions: a) private verbal emotional disclosure; b) clinician-assisted verbal emotional disclosure; c) arthritis information control (all of which engaged in four, 30-minute laboratory sessions); or d) no-treatment, standard care only control group. Outcome measures (pain, disability, affect, stress) were assessed at baseline, 2 months following treatment (2-month follow-up), and at 5-month, and 15-month follow-ups. A manipulation check demonstrated that, as expected, both types of emotional disclosure led to immediate (post-session) increases in negative affect compared with arthritis information. Outcome analyses at all three follow-ups revealed no clear pattern of effects for either clinician-assisted or private emotional disclosure compared with the two control groups. There were some benefits in terms of a reduction in pain behavior with private disclosure versus clinician-assisted disclosure at the 2 month follow-up, but no other significant between group differences. We conclude that verbal emotional disclosure about stressful experiences, whether conducted privately or assisted by a clinician, has little or no benefit for people with RA. PMID:17923329

Ottawa Panel Evidence-Based Clinical Practice Guidelines for Foot Care in the Management of Juvenile Idiopathic Arthritis.

PubMed

Brosseau, Lucie; Toupin-April, Karine; Wells, George; Smith, Christine A; Pugh, Arlanna G; Stinson, Jennifer N; Duffy, Ciarán M; Gifford, Wendy; Moher, David; Sherrington, Catherine; Cavallo, Sabrina; De Angelis, Gino; Loew, Laurianne; Rahman, Prinon; Marcotte, Rachel; Taki, Jade; Bisaillon, Jacinthe; King, Judy; Coda, Andrea; Hendry, Gordon J; Gauvreau, Julie; Hayles, Martin; Hayles, Kay; Feldman, Brian; Kenny, Glen P; Li, Jing Xian; Briggs, Andrew M; Martini, Rose; Feldman, Debbie Ehrmann; Maltais, Désirée B; Tupper, Susan; Bigford, Sarah; Bisch, Marg

2016-07-01

To create evidence-based guidelines evaluating foot care interventions for the management of juvenile idiopathic arthritis (JIA). An electronic literature search of the following databases from database inception to May 2015 was conducted: MEDLINE (Ovid), EMBASE (Ovid), Cochrane CENTRAL, and clinicaltrials.gov. The Ottawa Panel selection criteria targeted studies that assessed foot care or foot orthotic interventions for the management of JIA in those aged 0 to ≤18 years. The Physiotherapy Evidence Database scale was used to evaluate study quality, of which only high-quality studies were included (score, ≥5). A total of 362 records were screened, resulting in 3 full-text articles and 1 additional citation containing supplementary information included for the analysis. Two reviewers independently extracted study data (intervention, comparator, outcome, time period, study design) from the included studies by using standardized data extraction forms. Directed by Cochrane Collaboration methodology, the statistical analysis produced figures and graphs representing the strength of intervention outcomes and their corresponding grades (A, B, C+, C, C-, D+, D, D-). Clinical significance was achieved when an improvement of ≥30% between the intervention and control groups was present, whereas P>.05 indicated statistical significance. An expert panel Delphi consensus (≥80%) was required for the endorsement of recommendations. All included studies were of high quality and analyzed the effects of multidisciplinary foot care, customized foot orthotics, and shoe inserts for the management of JIA. Custom-made foot orthotics and prefabricated shoe inserts displayed the greatest improvement in pain intensity, activity limitation, foot pain, and disability reduction (grades A, C+). The use of customized foot orthotics and prefabricated shoe inserts seems to be a good choice for managing foot pain and function in JIA. Copyright © 2016 American Congress of Rehabilitation

Plasma miR-26a as a Diagnostic Biomarker Regulates Cytokine Expression in Systemic Juvenile Idiopathic Arthritis.

PubMed

Sun, Juan; Feng, Miao; Wu, Fengqi; Ma, Xiaolin; Lu, Jie; Kang, Min; Liu, Zhewei

2016-08-01

We sought to identify specific microRNA (miRNA) for systemic juvenile idiopathic arthritis (sJIA) and to determine the involvement of these miRNA in regulating the expression of cytokines. Microarray profiling was performed to identify differentially expressed miRNA in sJIA plasma. Levels of candidate miRNA and mRNA were assessed by real-time PCR, and cytokines were measured by ELISA. Dual-luciferase reporter assay was used to validate the direct interaction between miR-26a and interleukin 6 (IL-6). Forty-eight miRNA were differentially expressed in the plasma of patients with sJIA compared with healthy controls (HC). Five miRNA were selected for further validation. The expression level of miR-26a was exclusively elevated in the plasma of patients with sJIA as compared with 4 rheumatic diseases and 2 subtypes of JIA (oligoarticular and polyarticular). The levels of IL-6, IL-1β, and tumor necrosis factor-α in the plasma of patients with sJIA were increased, and only IL-6 presented a positive correlation with miR-26a (r = 0.539, p < 0.0001). After stimulation with IL-6, miR-26a expression was upregulated in THP-1 cells, while the supernatant level of IL-6 was downregulated by transfection of miR-26a mimics. Consistently, direct target relationship between miR-26a and IL-6 was confirmed. This study demonstrates that miR-26a is expressed specifically and highly in sJIA plasma and suggests that miR-26a may regulate the levels of cytokines in sJIA. Our findings highlight miR-26a as a potential biomarker for the diagnosis as well as differential diagnosis of sJIA.

Incidence and Prevalence of Juvenile Idiopathic Arthritis Among Children in a Managed Care Population, 1996–2009

PubMed Central

Harrold, Leslie R.; Salman, Craig; Shoor, Stanford; Curtis, Jeffrey R.; Asgari, Maryam M.; Gelfand, Joel M.; Wu, Jashin J.; Herrinton, Lisa J.

2017-01-01

Objective Few studies based in well-defined North American populations have examined the occurrence of juvenile idiopathic arthritis (JIA), and none has been based in an ethnically diverse population. We used computerized healthcare information from the Kaiser Permanente Northern California membership to validate JIA diagnoses and estimate the incidence and prevalence of the disease in this well-characterized population. Methods We identified children aged ≤ 15 years with ≥ 1 relevant International Classification of Diseases, 9th edition, diagnosis code of 696.0, 714, or 720 in computerized clinical encounter data during 1996–2009. In a random sample, we then reviewed the medical records to confirm the diagnosis and diagnosis date and to identify the best-performing case-finding algorithms. Finally, we used the case-finding algorithms to estimate the incidence rate and point prevalence of JIA. Results A diagnosis of JIA was confirmed in 69% of individuals with at least 1 relevant code. Forty-five percent were newly diagnosed during the study period. The age- and sex-standardized incidence rate of JIA per 100,000 person-years was 11.9 (95% CI 10.9–12.9). It was 16.4 (95% CI 14.6–18.1) in girls and 7.7 (95% CI 6.5–8.9) in boys. The peak incidence rate occurred in children aged 11–15 years. The prevalence of JIA per 100,000 persons was 44.7 (95% CI 39.1–50.2) on December 31, 2009. Conclusion The incidence rate of JIA observed in the Kaiser Permanente population, 1996–2009, was similar to that reported in Rochester, Minnesota, USA, but 2 to 3 times higher than Canadian estimates. PMID:23588938

Associations between interleukin-10 polymorphisms and susceptibility to juvenile idiopathic arthritis: a systematic review and meta-analysis.

PubMed

Harsini, Sara; Saghazadeh, Amene; Nedjat, Saharnaz; Rezaei, Nima

2018-03-01

Cytokine genes, including interleukin-10 (IL-10), are known to play important roles in the pathogenesis of juvenile idiopathic arthritis (JIA). This study aims to determine whether the IL-10 polymorphisms confer susceptibility to JIA. A meta-analysis was performed on the associations between the IL-10 -1082 G/A, -592 C/A, and -819 C/T polymorphisms and JIA. A total number of 7 studies involving 1,785 patients and 6,142 controls were considered in the meta-analysis. Meta-analysis of the IL-10 -592 C/A and -819 C/T polymorphisms showed no association with JIA in the study participants, or in Caucasian or Middle Eastern participants. Meta-analysis of the IL-10 -1082 A allele in all study participants, Caucasian and Middle Eastern, showed significant associations with RA (overall ORs were 1.17, 1.15, and 1.41, respectively). Meta-analysis of the AA versus GG genotype of the IL-10 -1082 G/A polymorphism revealed significant associations with JIA (OR = 3.66, 95% CI = 1.44-9.29, P = 0.006) in participants from Middle Eastern countries. Additionally, meta-analysis of the GG versus AA+GA genotypes of the IL-10 -1082 G/A polymorphism revealed the GG genotype as the protective factor against JIA in the Middle Eastern subgroup (OR = 0.44, 95% CI = 0.20-0.94, P = 0,04). Moreover, meta-analysis of the IL-10 -1082 A allele in 4 studies on Hardy-Weinberg equilibrium showed a significant association with JIA (OR = 1.17, 95% CI = 1.07-1.28, P = 0.0009). No association was found between the IL-10 (-1082, -819, -592) ACC, ATA, and GCC haplotypes and JIA. These results suggest that the IL-10 -1082 G/A polymorphism confers susceptibility to JIA.

Internet-based implementation of non-pharmacological interventions of the "people getting a grip on arthritis" educational program: an international online knowledge translation randomized controlled trial design protocol.

PubMed

Brosseau, Lucie; Wells, George; Brooks-Lineker, Sydney; Bennell, Kim; Sherrington, Cathie; Briggs, Andrew; Sturnieks, Daina; King, Judy; Thomas, Roanne; Egan, Mary; Loew, Laurianne; De Angelis, Gino; Casimiro, Lynn; Toupin April, Karine; Cavallo, Sabrina; Bell, Mary; Ahmed, Rukhsana; Coyle, Doug; Poitras, Stéphane; Smith, Christine; Pugh, Arlanna; Rahman, Prinon

2015-02-03

Rheumatoid arthritis (RA) affects 2.1% of the Australian population (1.5% males; 2.6% females), with the highest prevalence from ages 55 to over 75 years (4.4-6.1%). In Canada, RA affects approximately 0.9% of adults, and within 30 years that is expected to increase to 1.3%. With an aging population and a greater number of individuals with modifiable risk factors for chronic diseases, such as arthritis, there is an urgent need for co-care management of arthritic conditions. The increasing trend and present shifts in the health services and policy sectors suggest that digital information delivery is becoming more prominent. Therefore, it is necessary to further investigate the use of online resources for RA information delivery. The objective is to examine the effect of implementing an online program provided to patients with RA, the People Getting a Grip on Arthritis for RA (PGrip-RA) program, using information communication technologies (ie, Facebook and emails) in combination with arthritis health care professional support and electronic educational pamphlets. We believe this can serve as a useful and economical method of knowledge translation (KT). This KT randomized controlled trial will use a prospective randomized open-label blinded-endpoint design to compare four different intervention approaches of the PGrip-RA program to a control group receiving general electronic educational pamphlets self-management in RA via email. Depending on group allocation, links to the Arthritis Society PGrip-RA material will be provided either through Facebook or by email. One group will receive feedback online from trained health care professionals. The intervention period is 6 weeks. Participants will have access to the Internet-based material after the completion of the baseline questionnaires until the final follow-up questionnaire at 6 months. We will invite 396 patients from Canadian and Australian Arthritis Consumers' Associations to participate using online recruitment

Room for improvement: patient, parent, and practitioners' perceptions of foot problems and foot care in juvenile idiopathic arthritis.

PubMed

Hendry, Gordon J; Turner, Debbie E; Lorgelly, Paula K; Woodburn, James

2012-11-01

To explore the perceived impact of disease-related foot problems and foot care in juvenile idiopathic arthritis (JIA) from the perspectives of patients, parents, pediatric rheumatologists, and health professionals. A qualitative study using an interpretative phenomenological approach. Outpatients department, public health service children's hospital. Patients (N=15; 4 adult patients, 2 parents of children with JIA, 3 pediatric rheumatologists, and 6 health professionals) from 2 National Health Service rheumatology centers (1 pediatric and 1 adult). Not applicable. Qualitative outcomes were participants' perceptions elicited using semistructured interviews (telephone or face-to-face) and focus groups using an interpretative phenomenological approach. A data-driven inductive approach to coding and theme development was adopted for transcript analysis. Participants volunteered to take part in a total of 7 interviews and 2 focus groups. The analysis revealed 6 key themes related to the impact of foot problems and perceptions of foot care from respective groups. These were the following: (1) pain, (2) mobility impairment, (3) reduced ability to perform activities of daily living, (4) footwear difficulties, (5) poor referral pathways/delayed access to care, and (6) lack of evidence in support of conservative foot care. Several areas for development of foot care services were identified including a need for improved referral pathways, shorter waiting times for initial consultations, greater attention to patient compliance, and a need for better evidence in support of customized foot orthoses. Several key foot health-related outcomes were identified, which may be of importance for measuring therapeutic response to foot-related interventions. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Fatigue in children with juvenile idiopathic arthritis: reliability of the "Pediatric Quality of Life Inventory-Multidimensional Fatigue Scale".

PubMed

Paulo, Luciana Tudech S P; Len, Claudio A; Hilario, Maria Odete E; Pedroso, Soraya A; Vitalle, Maria Sylvia S; Terreri, Maria Teresa

2015-01-01

The aim of the study was (1) to translate the "Pediatric Quality of Life Inventory-Multidimensional Fatigue Scale" (PedsQL-Fatigue) into Brazilian Portuguese language and culture and evaluate its reliability and (2) to measure fatigue among patients with juvenile idiopathic arthritis (JIA): (1) Translation of the PedsQL-Fatigue by two bilingual researchers; (2) Backtranslation into English assessed by the authors of the original version; (3) Pilot study with five patients followed in the Pediatric Rheumatology Outpatient Clinic and their parents; and (4) Field study and assessment of measurement properties (internal consistency, reproducibility, and construct validity). In this stage, the scale was administered to 67 patients with JIA and 63 healthy individuals, aged from 2 to 18 years old, matched by age (from 2 to 4, 5 to 7, 8 to 12, and from 13 to 18 years old). Cronbach's alpha coefficient ranged from 0.6 to 0.8 for children and parents, indicating the instrument's good internal consistency. The scale's construct validity was confirmed by a satisfactory Spearman's coefficient between the PedsQL-Fatigue and the generic PedsQL 4.0 (0.840 for the children and 0.742 for the parents). Reproducibility was also adequate (0.764 for the children and 0.938 for the parents). No differences were found between the scores obtained by the JIA group and control group, though lower scores were observed among patients with clinically active JIA when compared to those without clinical activity. The PedsQL-Fatigue is a valid and reliable tool, and that can be used to measure fatigue among patients with JIA.

Treatment of idiopathic pulmonary fibrosis with losartan: a pilot project.

PubMed

Couluris, Marisa; Kinder, Brent W; Xu, Ping; Gross-King, Margaret; Krischer, Jeffrey; Panos, Ralph J

2012-10-01

Idiopathic pulmonary fibrosis is a progressive interstitial lung disease with no current effective therapies. Treatment has focused on antifibrotic agents to stop proliferation of fibroblasts and collagen deposition in the lung. We present the first clinical trial data on the use of losartan, an antifibrotic agent, to treat idiopathic pulmonary fibrosis. The primary objective was to evaluate the effect of losartan on progression of idiopathic pulmonary fibrosis measured by the change in percentage of predicted forced vital capacity (%FVC) after 12 months. Secondary outcomes included the change in forced expiratory volume at 1 second, diffusing capacity of carbon monoxide, 6-minute walk test distance, and baseline/transition dyspnea index. Patients with idiopathic pulmonary fibrosis and a baseline %FVC of ≥50 % were treated with losartan 50 mg by mouth daily for 12 months. Pulmonary function testing, 6-minute walk, and breathlessness indices were measured every 3 months. Twenty participants with idiopathic pulmonary fibrosis were enrolled and 17 patients were evaluable for response. Twelve patients had a stable or improved %FVC at study month 12. Similar findings were observed in secondary end-point measures, including 58, 71, and 65 % of patients with stable or improved forced expiratory volume at 1 second, diffusing capacity for carbon monoxide, and 6-minute walk test distance, respectively. No treatment-related adverse events that resulted in early study discontinuation were reported. Losartan stabilized lung function in patients with idiopathic pulmonary fibrosis over 12 months. Losartan is a promising agent for the treatment of idiopathic pulmonary fibrosis and has a low toxicity profile.

Novel method to collect medication adverse events in juvenile arthritis: results from the childhood arthritis and rheumatology research alliance enhanced drug safety surveillance project.

PubMed

Ringold, Sarah; Hendrickson, Audrey; Abramson, Leslie; Beukelman, Timothy; Blier, Peter R; Bohnsack, John; Chalom, Elizabeth C; Gewanter, Harry L; Gottlieb, Beth; Hollister, Roger; Hsu, Joyce; Hudgins, Andrea; Ilowite, Norman T; Klein-Gitelman, Marisa; Lindsley, Carol; Lopez Benitez, Jorge M; Lovell, Daniel J; Mason, Tom; Milojevic, Diana; Moorthy, Lakshmi N; Nanda, Kabita; Onel, Karen; Prahalad, Sampath; Rabinovich, C Egla; Ray, Linda; Rouster-Stevens, Kelly; Ruth, Natasha; Shishov, Michael; Spalding, Steven; Syed, Reema; Stoll, Matthew; Vehe, Richard K; Weiss, Jennifer E; White, Andrew J; Wallace, Carol A; Sobel, Rachel E

2015-04-01

Few data are available regarding the rates of serious adverse events (SAEs) and important medical events (IMEs) outside of product-based registries and clinical trials for juvenile idiopathic arthritis (JIA). The Enhanced Drug Safety Surveillance Project (EDSSP) was developed to pilot a novel system to collect SAEs/IMEs in children with JIA. This analysis reports the results from this 4-year (2008-2012) EDSSP. Participating physicians were surveyed monthly to ascertain whether their JIA patients experienced an SAE or IME. Sites were surveyed every 6 months to determine the number of unique JIA patients seen at each site during that 6-month period. Reporting rates were calculated per 100 person-years and 95% confidence intervals (95% CIs) were calculated based on a Poisson distribution. Thirty-seven Childhood Arthritis and Rheumatology Research Alliance sites with 115 physicians participated. The mean response rate to the monthly surveys was 65%. There were 147 total SAEs and 145 total IMEs. The largest proportion of SAEs and IMEs occurred in children with polyarticular JIA (39% and 37%, respectively). The majority of SAEs and IMEs were reported for patients receiving therapy with biologic agents (76% and 69%, respectively). The total event rate for SAEs and IMEs combined was 1.07 events per 100 person-years (95% CI 0.95-1.19). The rates for SAEs and IMEs were 0.54 per 100 person-years (95% CI 0.45-0.63) and 0.53 per 100 person-years (95% CI 0.49-0.62), respectively. The EDSSP provided a simple tool for SAE/IME reporting within an established research network and resulted in a similar range of reported events as captured by a traditional product-based registry. Copyright © 2015 by the American College of Rheumatology.

Placental villous hypermaturation is associated with idiopathic preterm birth

PubMed Central

Morgan, Terry K.; Tolosa, Jorge E.; Mele, Lisa; Wapner, Ronald J.; Spong, Catherine Y.; Sorokin, Yoram; Dudley, Donald J.; Peaceman, Alan M.; Mercer, Brian M.; Thorp, John M.; O’Sullivan, Mary Jo; Ramin, Susan M.; Rouse, Dwight J.; Sibai, Baha

2014-01-01

Objective Pregnancy complications such as intra-amniotic infection, preeclampsia, and fetal intrauterine growth restriction (IUGR) account for most cases of preterm birth (PTB), but many spontaneous PTB cases do not have a clear etiology. We hypothesize that placental insufficiency may be a potential cause of idiopathic PTB. Methods Secondary analysis of 82 placental samples from women with PTB obtained from a multicenter trial of repeat versus single antenatal corticosteroids. Samples were centrally reviewed by a single placental pathologist masked to clinical outcomes. The histopathologic criterion for infection was the presence of acute chorioamnionitis defined as neutrophils marginating into the chorionic plate. Placental villous hypermaturation (PVH) was defined as a predominance of terminal villi (similar to term placenta) with extensive syncytial knotting. Idiopathic PTB comprised a group without another known etiology such as preeclampsia, IUGR or infection. Results Acute chorioamnionitis was observed in 33/82 (40%) cases. Other known causes of PTB were reported in 18/82 (22%). The remaining 31/82 (38%) were idiopathic. The frequency of PVH in idiopathic PTB (26/31=84%) was similar to cases with IUGR or preeclampsia (16/ 18=89%), but significantly more common than PVH in the group with acute chorioamnionitis (10/33=30%) (p<0.001). Conclusions PVH, which is a histologic marker of relative placental insufficiency, is a common finding in idiopathic PTB. PMID:23130816

77 FR 39714 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-05

... Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the... Arthritis and Musculoskeletal and Skin Diseases, Special Emphasis Panel, Clinical Trials Applications. Date... of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, 6701 Democracy Blvd...

2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative.

PubMed

Ravelli, Angelo; Minoia, Francesca; Davì, Sergio; Horne, AnnaCarin; Bovis, Francesca; Pistorio, Angela; Aricò, Maurizio; Avcin, Tadej; Behrens, Edward M; De Benedetti, Fabrizio; Filipovic, Lisa; Grom, Alexei A; Henter, Jan-Inge; Ilowite, Norman T; Jordan, Michael B; Khubchandani, Raju; Kitoh, Toshiyuki; Lehmberg, Kai; Lovell, Daniel J; Miettunen, Paivi; Nichols, Kim E; Ozen, Seza; Pachlopnik Schmid, Jana; Ramanan, Athimalaipet V; Russo, Ricardo; Schneider, Rayfel; Sterba, Gary; Uziel, Yosef; Wallace, Carol; Wouters, Carine; Wulffraat, Nico; Demirkaya, Erkan; Brunner, Hermine I; Martini, Alberto; Ruperto, Nicolino; Cron, Randy Q

2016-03-01

To develop criteria for the classification of macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (JIA). A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of 28 experts was first asked to classify 428 patient profiles as having or not having MAS, based on clinical and laboratory features at the time of disease onset. The 428 profiles comprised 161 patients with systemic JIA-associated MAS and 267 patients with a condition that could potentially be confused with MAS (active systemic JIA without evidence of MAS, or systemic infection). Next, the ability of candidate criteria to classify individual patients as having MAS or not having MAS was assessed by evaluating the agreement between the classification yielded using the criteria and the consensus classification of the experts. The final criteria were selected in a consensus conference. Experts achieved consensus on the classification of 391 of the 428 patient profiles (91.4%). A total of 982 candidate criteria were tested statistically. The 37 best-performing criteria and 8 criteria obtained from the literature were evaluated at the consensus conference. During the conference, 82% consensus among experts was reached on the final MAS classification criteria. In validation analyses, these criteria had a sensitivity of 0.73 and a specificity of 0.99. Agreement between the classification (MAS or not MAS) obtained using the criteria and the original diagnosis made by the treating physician was high (κ=0.76). We have developed a set of classification criteria for MAS complicating systemic JIA and provided preliminary evidence of its validity. Use of these criteria will potentially improve understanding of MAS in systemic JIA and enhance efforts to discover effective therapies, by ensuring appropriate patient enrollment in studies. Published by the BMJ Publishing Group Limited. For permission to use (where not

Idiopathic anaphylaxis.

PubMed

Fenny, Nana; Grammer, Leslie C

2015-05-01

Idiopathic anaphylaxis is a diagnosis of exclusion after other causes have been thoroughly evaluated and excluded. The pathogenesis of idiopathic anaphylaxis remains uncertain, although increased numbers of activated lymphocytes and circulating histamine-releasing factors have been implicated. Signs and symptoms of patients diagnosed with idiopathic anaphylaxis are indistinguishable from the manifestations of other forms of anaphylaxis. Treatment regimens are implemented based on the frequency and severity of patient symptoms and generally include the use of epinephrine autoinjectors, antihistamines, and steroids. The prognosis of idiopathic anaphylaxis is generally favorable with well-established treatment regimens and effective patient education. Copyright © 2015 Elsevier Inc. All rights reserved.

Preventing progression from arthralgia to arthritis: targeting the right patients.

PubMed

van Steenbergen, Hanna W; da Silva, José A Pereira; Huizinga, Tom W J; van der Helm-van Mil, Annette H M

2018-01-01

Early treatment is associated with improved outcomes in patients with rheumatoid arthritis (RA), suggesting that a 'window of opportunity', in which the disease is most susceptible to disease-modifying treatment, exists. Autoantibodies and markers of systemic inflammation can be present long before clinical arthritis, and maturation of the immune response seems to coincide with the development of RA. The pre-arthritis phase associated with symptoms such as as joint pain without clinical arthritis (athralgia) is now hypothesized to fall within the aforementioned window of opportunity. Consequently, disease modulation in this phase might prevent the occurrence of clinically apparent arthritis, which would result in a persistent disease course if untreated. Several ongoing proof-of-concept trials are now testing this hypothesis. This Review highlights the importance of adequate risk prediction for the correct design, execution and interpretation of results of these prevention trials, as well as considerations when translating these findings into clinical practice. The patients' perspectives are discussed, and the accuracy with which RA development can be predicted in patients presenting with arthralgia is evaluated. Currently, the best starting position for preventive studies is proposed to be the inclusion of patients with an increased risk of RA, such as those identified as fulfilling the EULAR definition of 'arthralgia suspicious for progression to RA'.

Efficacy and adverse events of pirfenidone in treating idiopathic pulmonary fibrosis

PubMed Central

Ren, Hui; Wang, Kai; Yang, Hao; Gao, Lingyun

2017-01-01

Objectives: To analyze the efficacy and adverse events (AEs) of pirfenidone in idiopathic pulmonary fibrosis (IPF) trials. Methods: MEDLINE, Cochrane Library, and ClinicalTrials.gov were searched for studies published before June 2016. All studies of clinical trials with the key words IPF or idiopathic pulmonary fibrosis or lung fibrosis and pirfenidone or Esbriet were identified. Quality assessment and data extraction were conducted by 2 independent researchers. A meta-analysis of randomized controlled trials (RCTs) was performed, and relative risk (RR) and 95% confidence intervals (95% CIs) were calculated. Results: Five studies were included in this review, involving 1568 participants. The meta-analysis revealed that pirfenidone reduced the risk of decline in forced vital capacity (FVC)% ≥10% from baseline (relative risk: 0.62; 95% CI: 0.51-0.76, p<0.001). The pirfenidone group had a significantly higher rate of AEs compared with the placebo group. Pirfenidone did not reduce mortality from any cause significantly (odds ratio: 0.63; 95% CI: 0.36-1.09). Conclusions: This study showed that pirfenidone could reduce disease progression as assessed by the decline in FVC in IPF. Pirfenidone represents a suitable treatment option for patients with IPF. PMID:28889145

Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial.

PubMed

Raghu, Ganesh; Behr, Juergen; Brown, Kevin K; Egan, Jim J; Kawut, Steven M; Flaherty, Kevin R; Martinez, Fernando J; Nathan, Steven D; Wells, Athol U; Collard, Harold R; Costabel, Ulrich; Richeldi, Luca; de Andrade, Joao; Khalil, Nasreen; Morrison, Lake D; Lederer, David J; Shao, Lixin; Li, Xiaoming; Pedersen, Patty S; Montgomery, A Bruce; Chien, Jason W; O'Riordan, Thomas G

2013-05-07

Idiopathic pulmonary fibrosis (IPF) is characterized by formation and proliferation of fibroblast foci. Endothelin-1 induces lung fibroblast proliferation and contractile activity via the endothelin A (ETA) receptor. To determine whether ambrisentan, an ETA receptor-selective antagonist, reduces the rate of IPF progression. Randomized, double-blind, placebo-controlled, event-driven trial. (ClinicalTrials.gov: NCT00768300). Academic and private hospitals. Patients with IPF aged 40 to 80 years with minimal or no honeycombing on high-resolution computed tomography scans. Ambrisentan, 10 mg/d, or placebo. Time to disease progression, defined as death, respiratory hospitalization, or a categorical decrease in lung function. The study was terminated after enrollment of 492 patients (75% of intended enrollment; mean duration of exposure to study medication, 34.7 weeks) because an interim analysis indicated a low likelihood of showing efficacy for the end point by the scheduled end of the study. Ambrisentan-treated patients were more likely to meet the prespecified criteria for disease progression (90 [27.4%] vs. 28 [17.2%] patients; P = 0.010; hazard ratio, 1.74 [95% CI, 1.14 to 2.66]). Lung function decline was seen in 55 (16.7%) ambrisentan-treated patients and 19 (11.7%) placebo-treated patients (P = 0.109). Respiratory hospitalizations were seen in 44 (13.4%) and 9 (5.5%) patients in the ambrisentan and placebo groups, respectively (P = 0.007). Twenty-six (7.9%) patients who received ambrisentan and 6 (3.7%) who received placebo died (P = 0.100). Thirty-two (10%) ambrisentan-treated patients and 16 (10%) placebo-treated patients had pulmonary hypertension at baseline, and analysis stratified by the presence of pulmonary hypertension revealed similar results for the primary end point. The study was terminated early. Ambrisentan was not effective in treating IPF and may be associated with an increased risk for disease progression and respiratory hospitalizations. Gilead

Current treatment of juvenile rheumatoid arthritis.

PubMed

Ilowite, Norman T

2002-01-01

Prognostic factors in juvenile rheumatoid arthritis (JRA) include polyarticular onset, polyarticular disease course, and rheumatoid factor positivity; in the systemic onset subtype, persistence of systemic features at 6 months after onset confers a worse prognosis. Timely diagnosis and appropriate aggressive treatment of patients with poor prognostic features improve quality of life and outcome. After nonsteroidal anti-inflammatory drugs, methotrexate is the most commonly used second-line agent. However, approximately one third of patients do not respond to methotrexate adequately. Randomized, placebo-controlled, clinical trials in patients with JRA are few, but one such trial with the tumor necrosis factor inhibitor etanercept shows that this drug is effective and well-tolerated. Other recently approved agents for rheumatoid arthritis, including infliximab, leflunomide, celecoxib, and rofecoxib, have not been adequately studied in pediatric patients, and the role of these agents in children with JRA remains to be determined.

Pharmacokinetic and safety profile of tofacitinib in children with polyarticular course juvenile idiopathic arthritis: results of a phase 1, open-label, multicenter study.

PubMed

Ruperto, Nicolino; Brunner, Hermine I; Zuber, Zbigniew; Tzaribachev, Nikolay; Kingsbury, Daniel J; Foeldvari, Ivan; Horneff, Gerd; Smolewska, Elzbieta; Vehe, Richard K; Hazra, Anasuya; Wang, Rong; Mebus, Charles A; Alvey, Christine; Lamba, Manisha; Krishnaswami, Sriram; Stock, Thomas C; Wang, Min; Suehiro, Ricardo; Martini, Alberto; Lovell, Daniel J

2017-12-28

Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease and a leading cause of childhood disability. The objective of this study was to characterize the PK, safety, and taste acceptability of tofacitinib in patients with JIA. This Phase 1, open-label, multiple-dose (twice daily [BID] for 5 days) study of tofacitinib in patients with active (≥ 5 joints) polyarticular course JIA was conducted from March 2013-December 2015. Patients were allocated to one of three age-based cohorts: Cohort 1, 12 to < 18 years; Cohort 2, 6 to < 12 years; and Cohort 3, 2 to < 6 years. Tofacitinib was administered according to age and body weight as tablets or oral solution (grape flavor). PK were assessed on Day 5; safety was assessed at screening, Day 1, and Day 5. Taste acceptability of the oral solution was evaluated. Twenty-six patients (age range 2-17 years) were enrolled: Cohort 1, N = 8; Cohort 2, N = 9; Cohort 3, N = 9; median tofacitinib doses were 5.0, 2.5, and 3.0 mg BID, respectively. The higher median tofacitinib dose in Cohort 3 versus Cohort 2 reflected implementation of an amended dosing scheme following an interim PK analysis after Cohort 2 recruitment. Geometric mean AUC at steady state (AUC tau ) was 156.6 ng•h/mL in Cohort 1, 118.8 ng•h/mL in Cohort 2, and 142.5 ng•h/mL in Cohort 3; C max (ng/mL) was 47.0, 41.7, and 66.2, respectively. C trough , C min , and t 1/2 were similar in Cohorts 2 and 3, but higher in Cohort 1. Median time to C max (T max ) was similar between cohorts. Apparent clearance and volume of distribution decreased with decreasing age. Tofacitinib was well tolerated, with no serious adverse events or discontinuations due to adverse events reported. Taste acceptability was confirmed. PK findings from this study in children with polyarticular course JIA established dosing regimens and acceptable taste for use in subsequent studies within the tofacitinib pediatric development program

77 FR 64814 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-23

... Arthritis and Musculoskeletal and Skin Diseases Special Emphasis Panel; NIAMS clinical trial and planning grant applications in rheumatoid arthritis and skin diseases. Date: November 16, 2012. Time: 9:00 a.m... Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the...

Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

PubMed

Daily, James W; Yang, Mini; Park, Sunmin

2016-08-01

Although turmeric and its curcumin-enriched extracts have been used for treating arthritis, no systematic review and meta-analysis of randomized clinical trials (RCTs) have been conducted to evaluate the strength of the research. We systemically evaluated all RCTs of turmeric extracts and curcumin for treating arthritis symptoms to elucidate the efficacy of curcuma for alleviating the symptoms of arthritis. Literature searches were conducted using 12 electronic databases, including PubMed, Embase, Cochrane Library, Korean databases, Chinese medical databases, and Indian scientific database. Search terms used were "turmeric," "curcuma," "curcumin," "arthritis," and "osteoarthritis." A pain visual analogue score (PVAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were used for the major outcomes of arthritis. Initial searches yielded 29 articles, of which 8 met specific selection criteria. Three among the included RCTs reported reduction of PVAS (mean difference: -2.04 [-2.85, -1.24]) with turmeric/curcumin in comparison with placebo (P < .00001), whereas meta-analysis of four studies showed a decrease of WOMAC with turmeric/curcumin treatment (mean difference: -15.36 [-26.9, -3.77]; P = .009). Furthermore, there was no significant mean difference in PVAS between turmeric/curcumin and pain medicine in meta-analysis of five studies. Eight RCTs included in the review exhibited low to moderate risk of bias. There was no publication bias in the meta-analysis. In conclusion, these RCTs provide scientific evidence that supports the efficacy of turmeric extract (about 1000 mg/day of curcumin) in the treatment of arthritis. However, the total number of RCTs included in the analysis, the total sample size, and the methodological quality of the primary studies were not sufficient to draw definitive conclusions. Thus, more rigorous and larger studies are needed to confirm the therapeutic efficacy of turmeric for arthritis.

Idiopathic Ophthalmodynia and Idiopathic Rhinalgia: A Prospective Series of 16 New Cases.

PubMed

Pareja, Juan A; Montojo, Teresa; Guerrero, Ángel L; Álvarez, Mónica; Porta-Etessam, Jesús; Cuadrado, María L

2015-01-01

Idiopathic ophthalmodynia and idiopathic rhinalgia were described a few years ago. These conditions seem specific pain syndromes with a distinctive location in the eye or in the nose. We aimed to present a new prospective series in order to verify the consistency of these syndromes. We performed a descriptive study of all patients referred to our regional neurologic clinics from 2010 to 2014 because of facial pain exclusively felt in the eye or in the nose fulfilling the proposed diagnostic criteria for idiopathic ophthalmodynia and idiopathic rhinalgia. There were 9 patients with idiopathic ophthalmodynia and 7 patients with idiopathic rhinalgia, with a clear female preponderance, and a mean age at onset in the fifth decade. The pain was usually moderate and the temporal pattern was generally chronic. Only one patient reported accompaniments (hypersensitivity to the light and to the flow of air in the symptomatic eye). Preventive treatment with amitriptyline, pregabalin, or gabapentin was partially or totally effective. The clinical features of this new series parallels those of the original description, thus indicating that both idiopathic ophthalmodynia and idiopathic rhinalgia have clear-cut clinical pictures with excellent consistency both inter- and intra-individually. © 2015 American Headache Society.

Association of tumour necrosis factor-alpha G/A -238 and G/A -308 single nucleotide polymorphisms with juvenile idiopathic arthritis.

PubMed

Maddah, M; Harsini, S; Ziaee, V; Moradinejad, M H; Rezaei, A; Zoghi, S; Sadr, M; Aghighi, Y; Rezaei, N

2016-12-01

Juvenile idiopathic arthritis (JIA) is a heterogeneous autoimmune disorder of unknown origin. As proinflammatory cytokines are known to contribute towards the pathogenesis of JIA, this case-control study was performed to examine the associations of certain single nucleotide polymorphisms (SNPs) of tumour necrosis factor-α (TNF-α) gene. Fifty-three patients with JIA participated in this study as patients group and compared with 137 healthy unrelated controls. Genotyping was performed for TNF-α gene at positions -308 and -238, using polymerase chain reaction with sequence-specific primers method. Results of the analysed data revealed a significant positive association for TNF-α gene at positions -308 and -238 for A allele in patients group compared with controls (P < 0.01). At the genotypic level, the frequency of TNF-α gene at positions -308 and -238 for GG genotype was discovered to be higher in the patients with JIA compared to the healthy controls (P < 0.01), while GA genotype at the same positions was observed to be less frequent in the case group than the controls (P < 0.01). At the haplotypic level, a significant positive association for TNF-α GG haplotype (positions -308, -238) together with a notable negative association for TNF-α AG and GA haplotypes at the same positions were detected in the patients group in comparison with the healthy individuals (P < 0.01). Cytokine gene polymorphisms might affect the development of JIA. Particular TNF-α gene variants could render individuals more susceptible to JIA.. © 2016 John Wiley & Sons Ltd.

Long-Term Health-Related Quality of Life in German Patients with Juvenile Idiopathic Arthritis in Comparison to German General Population.

PubMed

Barth, Swaantje; Haas, Johannes-Peter; Schlichtiger, Jenny; Molz, Johannes; Bisdorff, Betty; Michels, Hartmut; Hügle, Boris; Radon, Katja

2016-01-01

Aims of the study were to investigate health-related quality of life (HRQOL) in adult patients with former diagnosis of Juvenile Idiopathic Arthritis (JIA), to compare their HRQOL with the general population and to identify factors related to a poor outcome. In 2012, a cross-sectional survey was performed by mailing a questionnaire to a large cohort of former and current patients of the German Centre for Rheumatology in Children and Adolescents. Only adult patients (≥18 years) with a diagnosis compatible with JIA were included (n = 2592; response 66%). The questionnaire included information about HRQOL (EQ5D), disease-related questions and socio-demographics. Prevalence and 95% confidence intervals (CI) of problems with mobility, self-care, usual activities, pain and anxiety/depression were standardized to the German general population. Factors associated with low HRQOL in JIA patients were identified using logistic regression models. Sixty-two percent of the study population was female; age range was 18-73 years. In all dimensions, JIA patients reported statistically significantly more problems than the general population with largest differences in the pain dimension (JIA patients 56%; 95%CI 55-58%; general population 28%; 26-29%) and the anxiety/depression dimension (28%; 27-29% vs. 4%; 4-5%). Lower HRQOL in JIA patients was associated with female sex, older age, lower level of education, still being under rheumatic treatment and disability. HRQOL in adult JIA patients is considerably lower than in the general population. As this cohort includes historic patients the new therapeutic schemes available today are expected to improve HRQOL in future.

78 FR 40486 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-05

... Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the... Arthritis and Musculoskeletal and Skin Diseases Special Emphasis Panel; Arthritis and Musculoskeletal and Skin Diseases Clinical Trials Conflict Review Meeting. Date: July 26, 2013. Time: 1:00 p.m. to 4:00 p.m...

A study of school adjustment, self-concept, self-esteem, general wellbeing and parent child relationship in Juvenile Idiopathic Arthritis.

PubMed

Yadav, Anita; Yadav, T P

2013-03-01

To assess school adjustment, self-concept, self-esteem, general wellbeing and parent-child relationship in children with Juvenile Idiopathic Arthritis (JIA)and to study the correlation of these parameters with chronicity of disease, number of active joints, laboratory parameters of disease activity and JIA subtypes. A total of 64 children (32 cases and 32 controls) were recruited for analysis. Self report questionnaires which included PGI General Wellbeing Measure, Adjustment Inventory for School Students, Parent Child Relationship Scale, Self Esteem Inventory and Self Concept Questionnaires were used to assess all the enrolled subjects. Cases had significantly lower general physical well being (p < 0.001), self- esteem (p = 0.039), social self-concept (p = 0.023) and poorer social (p = 0.002), educational (p = 0.002) and overall (p = 0.006) adjustment as compared to controls. Both parents of cases were significantly more demanding (p = 0.028, p = 0.004)and mothers were over protective (p = 0.009) and pampering with object rewards (p = 0.02). PGI wellbeing score (p = 0.042, p = 0.019) and self concept (p = 0.002, for social SCQ p = 0.030) correlated well with number of active joints and ESR. As the disease duration increased, fathers tended to neglect their children (p = 0.043) and with persistent disease activity (reflected by CRP positivity) even resorted to punishment (p = 0.022) or remained indifferent (p = 0.048). JIA significantly hampers the child's self-esteem, self-concept, adjustment in school, general wellbeing and evokes disturbed parent-child relationship.

Anti-inflammatory effects of polyphenols in arthritis.

PubMed

Oliviero, Francesca; Scanu, Anna; Zamudio-Cuevas, Yessica; Punzi, Leonardo; Spinella, Paolo

2018-03-01

Polyphenols have been extensively investigated with regard to their antioxidant, anti-inflammatory, and immunomodulant properties in many inflammatory chronic conditions. The aim of this review is to summarise how these compounds can modulate the inflammatory pathways which characterise the most prevalent arthropathies including osteoarthritis, rheumatoid arthritis and crystal-induced arthritis. Among polyphenols, epigallocatechin gallate, carnosol, hydroxytyrosol, curcumin, resveratrol, kaempferol and genistein have been the most widely investigated in arthritis. The most important results of the studies outlined in this article show how polyphenolic compounds are able to inhibit the expression and the release of a number of pro-inflammatory mediators and proteolytic enzymes, the activity of different transcriptional factors and the production of reactive oxygen species in vitro. Studies on animal models of rheumatoid arthritis, osteoarthritis and gout show interesting results in terms of reduced tissue damage, restored cartilage homeostasis, and decreased levels of uric acid, respectively. Despite the multiple protective effects of polyphenols, there are no dietary recommendations for patients affected by rheumatic diseases. Future studies, including intervention trials, should be conducted to determine the relevance of polyphenols consumption or supplementation in arthritis. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Idiopathic orthostatic hypotension treated with levodopa and MAO inhibitor: a preliminary report

PubMed Central

Sharpe, J.; Marquez-Julio, A.; Ashby, P.

1972-01-01

The clinical and pathophysiological features of a case of idiopathic orthostatic hypotension (Shy-Drager syndrome) are presented. Recent reports on the pathological findings in this condition indicate that there may be a defect in catecholamine synthesis in the pigmented brain stem nuclei and sympathetic ganglia similar to that in idiopathic parkinsonism. On this basis a new form of therapy using levodopa combined with MAO inhibition is derived. The results of a trial of this therapy, which produced improvements in both the hypotension and in the extrapyramidal features of the disease, are reported. PMID:5056115

The Effects of Aromatherapy Massage and Reflexology on Pain and Fatigue in Patients with Rheumatoid Arthritis: A Randomized Controlled Trial.

PubMed

Gok Metin, Zehra; Ozdemir, Leyla

2016-04-01

Nonpharmacologic interventions for symptom management in patients with rheumatoid arthritis are underinvestigated. Limited data suggest that aromatherapy massage and reflexology may help to reduce pain and fatigue in patients with rheumatoid arthritis. The aim of this study was to examine and compare the effects of aromatherapy massage and reflexology on pain and fatigue in patients with rheumatoid arthritis. The study sample was randomly assigned to either an aromatherapy massage (n = 17), reflexology (n = 17) or the control group (n = 17). Aromatherapy massage was applied to both knees of subjects in the first intervention group for 30 minutes. Reflexology was administered to both feet of subjects in the second intervention group for 40 minutes during weekly home visits. Control group subjects received no intervention. Fifty-one subjects with rheumatoid arthritis were recruited from a university hospital rheumatology clinic in Turkey between July 2014 and January 2015 for this randomized controlled trial. Data were collected by personal information form, DAS28 index, Visual Analog Scale and Fatigue Severity Scale. Pain and fatigue scores were measured at baseline and within an hour after each intervention for 6 weeks. Pain and fatigue scores significantly decreased in the aromatherapy massage and reflexology groups compared with the control group (p < .05). The reflexology intervention started to decrease mean pain and fatigue scores earlier than aromatherapy massage (week 1 vs week 2 for pain, week 1 vs week 4 for fatigue) (p < .05). Aromatherapy massage and reflexology are simple and effective nonpharmacologic nursing interventions that can be used to help manage pain and fatigue in patients with rheumatoid arthritis. Copyright © 2016 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Efficacy and adverse events of pirfenidone in treating idiopathic pulmonary fibrosis.

PubMed

Ren, Hui; Wang, Kai; Yang, Hao; Gao, Lingyun

2017-09-01

To analyze the efficacy and adverse events  (AEs) of pirfenidone in idiopathic pulmonary fibrosis (IPF) trials. Methods: MEDLINE, Cochrane Library, and ClinicalTrials.gov were searched for studies published before June 2016. All studies of clinical trials with the key words IPF or idiopathic pulmonary fibrosis or lung fibrosis and pirfenidone or Esbriet were identified. Quality assessment and data extraction nwere conducted by 2 independent researchers. A meta-analysis of randomized controlled trials (RCTs) was performed, and relative risk (RR) and 95% confidence intervals (95% CIs) were calculated.   Results: Five studies were included in this review, involving 1568 participants. The meta-analysis revealed that pirfenidone reduced the risk of decline in forced vital capacity (FVC)% ≥10% from baseline (relative risk: 0.62; 95% CI: 0.51-0.76, p less than 0.001). The pirfenidone group had a significantly higher rate of AEs compared with the placebo group. Pirfenidone did not reduce mortality from any cause significantly (odds ratio: 0.63; 95% CI: 0.36-1.09). Conclusions: This study showed that pirfenidone could reduce disease progression as assessed by the decline in FVC in IPF. Pirfenidone represents a suitable treatment option for patients with IPF.

Improvement of reduced serum cartilage oligomeric matrix protein levels in systemic juvenile idiopathic arthritis patients treated with the anti-interleukin-6 receptor monoclonal antibody tocilizumab.

PubMed

Nakajima, Shoko; Naruto, Takuya; Miyamae, Takako; Imagawa, Tomoyuki; Mori, Masaaki; Nishimaki, Shigeru; Yokota, Shumpei

2009-01-01

In this study, we determined serum cartilage oligomeric matrix protein (COMP) levels in systemic juvenile idiopathic arthritis (sJIA) patients during both the active and the remission phases to investigate how the growth cartilage turnover changed under tocilizumab treatment. Specimens were collected from 201 healthy children under 16 years of age with no growth impairment, and paired sera were collected from 11 sJIA patients treated with tocilizumab. Disease activity was assessed from white blood cell count, erythrocyte sedimentation rate, C-reactive protein, and ferritin, and the COMP concentration was determined by sandwich enzyme-linked immunosorbent assay. Serum COMP concentrations were found independent of age, and the mean value in healthy children was 17.74+/-5.6 U/L. The mean serum COMP in sJIA patients during the active phase was 10.75+/-3.9 U/L, lower than that of healthy children. The mean serum COMP in the remission phase (14.89+/-3.9 U/L) was significantly higher than that in the active period (P<0.05). These results suggested that in sJIA patients, a reduced serum COMP concentration is a useful marker of active disease and growth impairment, and that the growth cartilage turnover suppressed during the active phase is improved in the remission phase under tocilizumab treatment.

A randomised controlled trial of occupational therapy for people with early rheumatoid arthritis.

PubMed

Hammond, A; Young, A; Kidao, R

2004-01-01

Occupational therapy (OT) aims at improving performance of daily living tasks, facilitating successful adjustments in lifestyle, and preventing losses of function. To evaluate the effects of a pragmatic, comprehensive OT programme on self management and health status of people with early rheumatoid arthritis (RA) (<2.5 years). A randomised, controlled "assessor blinded" trial was conducted with assessments made at entry, 6, 12, and 24 months. Main outcomes were AIMS2: physical function (PF), pain visual analogue scale (VAS), and Arthritis Self-Efficacy Scale (ASES). Groups had similar disease duration (9 months OT (n = 162) v 10 months control (n = 164)). The OT group received 7.57 (SD 3.04) hours of therapy. Self management significantly increased in the OT group. Otherwise, there were no significant differences in any outcome measures, or between groups, by ACR functional class: AIMS2: PF (F = 0.04; p = 0.96); pain VAS (F = 0.29; p = 0.74); total ASES score (F = 0.93; p = 0.39). OT improved self management but not health status in early RA. Functional ability remains reasonably good for many in the first five years, so preventive benefits of self management may not yet be apparent and longer follow up is needed. Although many considered the education and therapy useful, insufficient numbers in the OT group used self management sufficiently to make a difference. Behavioural approaches can improve adherence and, potentially, the long term benefits. Future research should evaluate OT as a complex intervention and develop programmes from a theoretical and evidence base.

Brief report: enhancement of patient recruitment in rheumatoid arthritis clinical trials using a multi-biomarker disease activity score as an inclusion criterion.

PubMed

van Vollenhoven, Ronald F; Bolce, Rebecca; Hambardzumyan, Karen; Saevarsdottir, Saedis; Forslind, Kristina; Petersson, Ingemar F; Sasso, Eric H; Hwang, C C; Segurado, Oscar G; Geborek, Pierre

2015-11-01

Rheumatoid arthritis (RA) clinical trials often exclude patients who have low C-reactive protein (CRP) levels, which slows enrollment into the trial. The purpose of this study was to determine whether high Multi-Biomarker Disease Activity (MBDA) scores (>44) in RA patients with low CRP levels (≤10 mg/liter) could be used as a complement to CRP levels >10 mg/liter to enhance patient recruitment without affecting clinical trial outcomes. We evaluated patients from the Swedish Pharmacotherapy (SWEFOT) trial, which did not include any selection criteria for CRP levels. Clinical outcomes were assessed after 3 months of methotrexate (MTX) monotherapy in MTX-naive RA patients (n = 220) and after 3-10 months of add-on therapy in patients who were incomplete responders to MTX alone (MTX-IR) (n = 127). Radiographic outcomes were assessed at 1 year in all patients. Within each cohort, the outcomes were compared between patients with a CRP level of ≤10 mg/liter and an MBDA score of >44 at the start of the respective treatment interval versus those with a CRP level of >10 mg/liter. Patients with both a CRP level of ≤10 mg/liter and an MBDA score of >44 at baseline had clinical and radiographic outcomes that were comparable to those in patients with a CRP level of >10 mg/liter at baseline. This broadened definition of the inclusion criteria identified an additional 24% of patients in the MTX-naive cohort and 47% in the MTX-IR cohort. Patient recruitment into RA clinical trials may be substantially enhanced, without any decrease in clinical and radiographic outcomes, by using as an inclusion criterion "a CRP level of >10 mg/liter and/or an MBDA score of >44." © 2015 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

Lubiprostone: a new drug for the treatment of chronic idiopathic constipation.

PubMed

Baker, Danial E

2007-01-01

Lubiprostone offers an additional alternative for patients with chronic idiopathic constipation. Lubiprostone is more efficacious than placebo in the treatment of chronic idiopathic constipation. In placebo-controlled clinical trials, lubiprostone therapy was generally well tolerated and was not associated with severe adverse effects; however, the high incidence of nausea may be problematic for some patients. The nausea may be alleviated or minimized by administering the dose with food, and some patients may require a dosage reduction to 24 mug once daily. The key limitations of the placebo-controlled clinical trials include the absence of information regarding the duration of the constipation and previous types of therapies that had been used to treat the constipation and the absence of an active control group. Comparative studies with other therapies (eg, saline laxatives, polyethylene glycol) used for constipation are necessary to determine the clinical and economic value of this agent relative to other forms of therapy.

Arthritis - resources

MedlinePlus

Resources - arthritis ... The following organizations provide more information on arthritis : American Academy of Orthopaedic Surgeons -- orthoinfo.aaos.org/menus/arthritis.cfm Arthritis Foundation -- www.arthritis.org Centers for Disease Control and Prevention -- www. ...

Advances in the management of rheumatoid arthritis.

PubMed

Dale, James

2015-08-01

Modern early rheumatoid arthritis strategies are usually based upon a number of important overarching principles: 1. early diagnosis facilitates early commencement of disease modifying anti-rheumatic therapy; 2. early commencement of treatment reduces the long-term risk of erosive damage and functional decline; 3. composite disease activity measures should be used to quantify global rheumatoid arthritis disease activity; and 4. therapy should be intensified until a predefined disease activity target has been achieved. A substantial minority of rheumatoid arthritis patients (approximately 40%) will experience an adequate response to methotrexate monotherapy; however, the remainder may require disease modifying anti-rheumatic combination therapy, and/or biologic therapy, to achieve disease activity targets. Importantly, short term trials of methotrexate monotherapy do not appear to disadvantage outcomes provided treatment continues to be intensified if disease activity targets are not achieved. © The Author(s) 2015.

Influence of polymorphisms within the methotrexate pathway genes on the toxicity and efficacy of methotrexate in patients with juvenile idiopathic arthritis.

PubMed

Yanagimachi, Masakatsu; Naruto, Takuya; Hara, Takuma; Kikuchi, Masako; Hara, Ryoki; Miyamae, Takako; Imagawa, Tomoyuki; Mori, Masaaki; Kaneko, Tetsuji; Morita, Satoshi; Goto, Hiroaki; Yokota, Shumpei

2011-02-01

We investigated whether several polymorphisms within the methotrexate (MTX) pathway genes were related to the toxicity and efficacy of MTX in 92 Japanese patients with articular-type juvenile idiopathic arthritis (JIA). Eight gene polymorphisms within the MTX pathway genes, namely, RFC, BCRP, MTHFR (two), FPGS, γ-glutamyl hydrolase (GGH; two) and ATIC, were genotyped using TaqMan assays. Liver dysfunction was defined as an increase in alanine transaminase to five times the normal upper limit. Non-responders to MTX were defined as patients refractory to MTX and were therefore treated with biologics. The non-TT genotype at GGH T16C was associated with a high risk of liver dysfunction (P=0.028, odds ratio=6.90, 95% confidence interval 1.38-34.5), even after adjustment for the duration of MTX treatment. A longer interval from disease onset to treatment (8.5 and 21.3 months, P=0.029) and rheumatoid factor positivity (P=0.026, odds ratio=2.87, 95% confidence interval 1.11-7.39) were associated with lower efficacy of MTX. The non-TT genotype at GGH T16C was associated with a high risk of liver dysfunction, presumably because the C allele of GGH C16T may reduce the activity of GGH. The time interval before MTX treatment and rheumatoid factor positivity were associated with the efficacy of MTX treatment. The pharmacogenetics of the MTX pathway genes affects the toxicity and efficacy of MTX in Japanese JIA patients. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Influence of polymorphisms within the methotrexate pathway genes on the toxicity and efficacy of methotrexate in patients with juvenile idiopathic arthritis

PubMed Central

Yanagimachi, Masakatsu; Naruto, Takuya; Hara, Takuma; Kikuchi, Masako; Hara, Ryoki; Miyamae, Takako; Imagawa, Tomoyuki; Mori, Masaaki; Kaneko, Tetsuji; Morita, Satoshi; Goto, Hiroaki; Yokota, Shumpei

2011-01-01

AIMS We investigated whether several polymorphisms within the methotrexate (MTX) pathway genes were related to the toxicity and efficacy of MTX in 92 Japanese patients with articular-type juvenile idiopathic arthritis (JIA). METHODS Eight gene polymorphisms within the MTX pathway genes, namely, RFC, BCRP, MTHFR (two), FPGS, γ-glutamyl hydrolase (GGH; two) and ATIC, were genotyped using TaqMan assays. Liver dysfunction was defined as an increase in alanine transaminase to five times the normal upper limit. Non-responders to MTX were defined as patients refractory to MTX and were therefore treated with biologics. RESULTS The non-TT genotype at GGH T16C was associated with a high risk of liver dysfunction (P = 0.028, odds ratio = 6.90, 95% confidence interval 1.38–34.5), even after adjustment for the duration of MTX treatment. A longer interval from disease onset to treatment (8.5 and 21.3 months, P = 0.029) and rheumatoid factor positivity (P = 0.026, odds ratio = 2.87, 95% confidence interval 1.11–7.39) were associated with lower efficacy of MTX. CONCLUSIONS The non-TT genotype at GGH T16C was associated with a high risk of liver dysfunction, presumably because the C allele of GGH C16T may reduce the activity of GGH. The time interval before MTX treatment and rheumatoid factor positivity were associated with the efficacy of MTX treatment. The pharmacogenetics of the MTX pathway genes affects the toxicity and efficacy of MTX in Japanese JIA patients. PMID:21219404

Long-Term Health-Related Quality of Life in German Patients with Juvenile Idiopathic Arthritis in Comparison to German General Population

PubMed Central

Barth, Swaantje; Haas, Johannes-Peter; Schlichtiger, Jenny; Molz, Johannes; Bisdorff, Betty; Michels, Hartmut; Hügle, Boris; Radon, Katja

2016-01-01

Objective Aims of the study were to investigate health-related quality of life (HRQOL) in adult patients with former diagnosis of Juvenile Idiopathic Arthritis (JIA), to compare their HRQOL with the general population and to identify factors related to a poor outcome. Methods In 2012, a cross-sectional survey was performed by mailing a questionnaire to a large cohort of former and current patients of the German Centre for Rheumatology in Children and Adolescents. Only adult patients (≥18 years) with a diagnosis compatible with JIA were included (n = 2592; response 66%). The questionnaire included information about HRQOL (EQ5D), disease-related questions and socio-demographics. Prevalence and 95% confidence intervals (CI) of problems with mobility, self-care, usual activities, pain and anxiety/depression were standardized to the German general population. Factors associated with low HRQOL in JIA patients were identified using logistic regression models. Results Sixty-two percent of the study population was female; age range was 18–73 years. In all dimensions, JIA patients reported statistically significantly more problems than the general population with largest differences in the pain dimension (JIA patients 56%; 95%CI 55–58%; general population 28%; 26–29%) and the anxiety/depression dimension (28%; 27–29% vs. 4%; 4–5%). Lower HRQOL in JIA patients was associated with female sex, older age, lower level of education, still being under rheumatic treatment and disability. Conclusions HRQOL in adult JIA patients is considerably lower than in the general population. As this cohort includes historic patients the new therapeutic schemes available today are expected to improve HRQOL in future. PMID:27115139

Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

PubMed Central

Daily, James W.; Yang, Mini

2016-01-01

Abstract Although turmeric and its curcumin-enriched extracts have been used for treating arthritis, no systematic review and meta-analysis of randomized clinical trials (RCTs) have been conducted to evaluate the strength of the research. We systemically evaluated all RCTs of turmeric extracts and curcumin for treating arthritis symptoms to elucidate the efficacy of curcuma for alleviating the symptoms of arthritis. Literature searches were conducted using 12 electronic databases, including PubMed, Embase, Cochrane Library, Korean databases, Chinese medical databases, and Indian scientific database. Search terms used were “turmeric,” “curcuma,” “curcumin,” “arthritis,” and “osteoarthritis.” A pain visual analogue score (PVAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were used for the major outcomes of arthritis. Initial searches yielded 29 articles, of which 8 met specific selection criteria. Three among the included RCTs reported reduction of PVAS (mean difference: −2.04 [−2.85, −1.24]) with turmeric/curcumin in comparison with placebo (P < .00001), whereas meta-analysis of four studies showed a decrease of WOMAC with turmeric/curcumin treatment (mean difference: −15.36 [−26.9, −3.77]; P = .009). Furthermore, there was no significant mean difference in PVAS between turmeric/curcumin and pain medicine in meta-analysis of five studies. Eight RCTs included in the review exhibited low to moderate risk of bias. There was no publication bias in the meta-analysis. In conclusion, these RCTs provide scientific evidence that supports the efficacy of turmeric extract (about 1000 mg/day of curcumin) in the treatment of arthritis. However, the total number of RCTs included in the analysis, the total sample size, and the methodological quality of the primary studies were not sufficient to draw definitive conclusions. Thus, more rigorous and larger studies are needed to confirm the therapeutic efficacy

The impact of disease activity and tumour necrosis factor-α inhibitor therapy on cytokine levels in juvenile idiopathic arthritis.

PubMed

Walters, H M; Pan, N; Lehman, T J A; Adams, A; Kalliolias, G D; Zhu, Y S; Santiago, F; Nguyen, J; Sitaras, L; Cunningham-Rundles, S; Walsh, T J; Toussi, S S

2016-06-01

The aim of this study was to evaluate prospectively cytokine levels and disease activity in juvenile idiopathic arthritis (JIA) patients treated with and without tumour necrosis factor (TNF)-α inhibitors. TNF-α inhibitor-naive JIA subjects were followed prospectively for 6 months. Cytokine levels of TNF-α, interleukin (IL)-1β, IL-6, IL-8, IL-10 and IL-17 were measured at baseline for JIA subjects and healthy controls (HCs). Cytokine levels were then measured at four time-points after initiation of TNF-α inhibition for anti-TNF-α-treated (anti-TNF) JIA subjects, and at two subsequent time-points for other JIA (non-TNF) subjects. JIA disease activity by Childhood Health Assessment Questionnaire (CHAQ) disability index/pain score and physician joint count/global assessment was recorded. Sixteen anti-TNF, 31 non-TNF and 16 HCs were analysed. Among JIA subjects, those with higher baseline disease activity (subsequent anti-TNFs) had higher baseline TNF-α, IL-6 and IL-8 than those with lower disease activity (non-TNFs) (P < 0·05). TNF-α and IL-10 increased, and IL-6 and IL-8 no longer remained significantly higher after TNF-α inhibitor initiation in anti-TNF subjects. Subgroup analysis of etanercept versus adalimumab-treated subjects showed that TNF-α and IL-17 increased significantly in etanercept but not adalimumab-treated subjects, despite clinical improvement in both groups of subjects. JIA subjects with increased disease activity at baseline had higher serum proinflammatory cytokines. TNF-α inhibition resulted in suppression of IL-6 and IL-8 in parallel with clinical improvement in all anti-TNF-treated subjects, but was also associated with elevated TNF-α and IL-17 in etanercept-treated subjects. © 2016 British Society for Immunology.

Significant IFNγ responses of CD8+ T cells in CMV-seropositive individuals with autoimmune arthritis.

PubMed

Almanzar, Giovanni; Schmalzing, Marc; Trippen, Raimund; Höfner, Kerstin; Weißbrich, Benedikt; Geissinger, Eva; Meyer, Thomas; Liese, Johannes; Tony, Hans-Peter; Prelog, Martina

2016-04-01

Latent Cytomegalovirus (CMV) infection accelerates immunosenescence in elderly with reactivations reported in Rheumatoid Arthritis (RA) and abnormal responses towards CMV in Juvenile Idiopathic Arthritis (JIA). Considering the signs of premature T-cell immunosenescence in arthritis patients, the known effect of CMV latency on speeding up many of these signs in an age-dependent manner and the role of CMV on IFNγ-mediated inflammation in healthy elderly and RA, we hypothesized that latent CMV infection accelerates TCR repertoire restriction, loss of CD28, peripheral T-cell proliferation and aberrant IFNγ responses in arthritis patients. Unspecific and CMVpp65-specific IFNγ responses were investigated in peripheral CD8+ T-cells in RA or JIA patients and healthy, age-matched controls. Despite higher prevalence and concentrations of IgG-anti-CMV, arthritis patients showed lower unspecific IFNγ production, lower CD69-mediated activation and lower CD8+ T-cell proliferation. CMV-seropositive RA patients showed higher intracellular IFNγ production and increased proportions of CD28-CD8+ T-cells after specific CMVpp65 long-term stimulation which was not altered by in vitro blockade of TNFα or IL-6. A skewed TCR repertoire towards oligoclonality and less polyclonality was found in JIA. CMVpp65-specific IFNγ production with expansion of CD28-CD8+ T-cells suggests an efficient control of latent CMV regardless of immunosuppressive therapy or in vitro blockade of TNFα or IL-6 in CMV-seropositive arthritis patients. Increased IgG-anti-CMV antibody concentrations and increased proportions of intracellular IFNγ-producing CMVpp65-specific CD8+ T-cells in long-term cultures propose a possibly role of endogenous CMV reactivations boosting antibody levels and a higher possibly CMV-driven IFNγ-mediated inflammatory potential of CD8+ T-cells in arthritis patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Subgroup analysis of Asian patients in the INPULSIS® trials of nintedanib in idiopathic pulmonary fibrosis.

PubMed

Taniguchi, Hiroyuki; Xu, Zuojun; Azuma, Arata; Inoue, Yoshikazu; Li, Huiping; Fujimoto, Tsuyoshi; Bailes, Zelie; Schlenker-Herceg, Rozsa; Kim, Dong S

2016-11-01

In the two-replicate randomized Phase III INPULSIS® trials in patients with idiopathic pulmonary fibrosis (IPF), nintedanib 150 mg bd significantly reduced the annual rate of decline in forced vital capacity (FVC) compared with placebo. The key secondary endpoints were time to first investigator-reported acute exacerbation and change from baseline in St George's Respiratory Questionnaire total score, both over 52 weeks. Here, we assessed the effect of nintedanib in Asian patients. Pre-specified subgroup analyses of the effect of nintedanib on the primary and key secondary endpoints in Asian versus White patients were undertaken based on pooled data from the two INPULSIS® trials. Safety data were analyzed descriptively. Of the treated patients, 322 were Asian (nintedanib n = 194; placebo n = 128) and 608 were White (nintedanib n = 360; placebo n = 248). In Asian patients, the nintedanib versus placebo difference in the adjusted annual rate of decline in FVC was 94.1 mL/year (95% CI: 33.7, 154.6). The treatment effect of nintedanib on the annual rate of decline in FVC in Asian and White patients was similar (treatment-by-subgroup interaction P = 0.72) and consistent with the overall population. No significant treatment-by-subgroup interaction was observed for the key secondary endpoints between Asian and White patients. In Asian patients, the most common adverse event in the nintedanib group was diarrhoea (56.2% of patients vs 15.6% for placebo). In pre-specified subgroup analyses of Asian versus White patients with IPF in the INPULSIS® trials, race did not influence the effect of nintedanib on disease progression. © 2016 Asian Pacific Society of Respirology.

Photographic Reading Center of the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT): Methods and Baseline Results

PubMed Central

Fischer, William S.; Wall, Michael; McDermott, Michael P.; Kupersmith, Mark J.; Feldon, Steven E.

2015-01-01

Purpose. To describe the methods used by the Photographic Reading Center (PRC) of the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) and to report baseline assessments of papilledema severity in participants. Methods. Stereoscopic digital images centered on the optic disc and the macula were collected using certified personnel and photographic equipment. Certification of the camera system included standardization and calibration using a model eye. Lay readers assessed disc photos of all eyes using the Frisén grade and performed quantitative measurements of papilledema. Frisén grades by PRC were compared with site investigator clinical grades. Spearman rank correlations were used to quantify associations among disc features and selected clinical variables. Results. Frisén grades according to the PRC and site investigator's grades, matched exactly in 48% of the study eyes and 42% of the fellow eyes and within one grade in 94% of the study eyes and 92% of the fellow eyes. Frisén grade was strongly correlated (r > 0.65, P < 0.0001) with quantitative measures of disc area. Cerebrospinal fluid pressure was weakly associated with Frisén grade and disc area determinations (r ≤ 0.31). Neither Frisén grade nor any fundus feature was associated with perimetric mean deviation. Conclusions. In a prospective clinical trial, lay readers agreed reasonably well with physicians in assessing Frisén grade. Standardization of camera systems enhanced consistency of photographic quality across study sites. Images were affected more by sensors with poor dynamic range than by poor resolution. Frisén grade is highly correlated with quantitative assessment of disc area. (ClinicalTrials.gov number, NCT01003639.) PMID:26024112

Photographic Reading Center of the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT): Methods and Baseline Results.

PubMed

Fischer, William S; Wall, Michael; McDermott, Michael P; Kupersmith, Mark J; Feldon, Steven E

2015-05-01

To describe the methods used by the Photographic Reading Center (PRC) of the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) and to report baseline assessments of papilledema severity in participants. Stereoscopic digital images centered on the optic disc and the macula were collected using certified personnel and photographic equipment. Certification of the camera system included standardization and calibration using a model eye. Lay readers assessed disc photos of all eyes using the Frisén grade and performed quantitative measurements of papilledema. Frisén grades by PRC were compared with site investigator clinical grades. Spearman rank correlations were used to quantify associations among disc features and selected clinical variables. Frisén grades according to the PRC and site investigator's grades, matched exactly in 48% of the study eyes and 42% of the fellow eyes and within one grade in 94% of the study eyes and 92% of the fellow eyes. Frisén grade was strongly correlated (r > 0.65, P < 0.0001) with quantitative measures of disc area. Cerebrospinal fluid pressure was weakly associated with Frisén grade and disc area determinations (r ≤ 0.31). Neither Frisén grade nor any fundus feature was associated with perimetric mean deviation. In a prospective clinical trial, lay readers agreed reasonably well with physicians in assessing Frisén grade. Standardization of camera systems enhanced consistency of photographic quality across study sites. Images were affected more by sensors with poor dynamic range than by poor resolution. Frisén grade is highly correlated with quantitative assessment of disc area. (ClinicalTrials.gov number, NCT01003639.).

[Insight into the training of patients with idiopathic inflammatory myopathy].

PubMed

Váncsa, Andrea

2016-09-01

Using current recommended treatment, a majority of patients with idiopathic inflammatory myopathy develop muscle impairment and poor health. Beneficial effects of exercise have been reported on muscle performance, aerobic capacity and health in chronic polymyositis and dermatomyositis, as well as in active disease and inclusion body myositis to some extent. Importantly, randomized controlled trials indicate that improved health and decreased clinical disease activity could be mediated through increased aerobic capacity. Recently, reports seeking pathomechanisms of the underlying effects of exercise on skeletal muscle indicate increased aerobic capacity (i.e. increased mitochondrial capacity and capillary density, reduced lactate levels), activation of genes of aerobic phenotype and muscle growth programs and down regulation of genes related to inflammation. Exercise contributes to both systemic and within-muscle adaptations demonstrating that it is fundamental for improving muscle performance and health in patients with idiopathic inflammatory myopathy. There is a need for randomized controlled trials to study the effects of exercise in patients with active disease and inclusion body myositis. Orv. Hetil., 2016, 157(39), 1557-1562.

Decreased PD-1 expression on circulating CD4+T cell and PD-L1 expression on myeloid dendritic cell correlate with clinical manifestations in systemic juvenile idiopathic arthritis.

PubMed

Cai, Li; Zhang, Chenxing; Wu, Jing; Zhou, Wei; Chen, Tongxin

2018-03-30

Programmed cell death-1 (PD-1) and its ligand (PD-L1) mediate negative signal in autoimmune diseases. While little is known about its role in juvenile idiopathic arthritis (JIA). The study aimed to reveal the circulating cell profile and the relative PD-1/PD-L1 expression of JIA subsets, elucidating their underlying immunomodulatory mechanisms. We detected the circulating cells and the relative PD-1/PD-L1 signaling in 101 JIA patients and 50 controls by flow cytometry and analyzed their association with disease activity and clinical manifestations. Different from other JIA types, active systemic JIA (sJIA) patients had lower percentage and count of CD4 + T cells and lower PD-1 expression on them compared with healthy controls (P<0.05), active polyarthritis (P<0.05) and enthesitis-related arthritis (ERA) patients (P<0.05). Also, they had higher percentage and count of myeloid dendritic cell (mDC) and lower PD-L1 expression on mDC compared with healthy controls (P<0.05). Both PD-1 on CD4 + T cell and PD-L1 on mDC were negatively correlated with JADAS-27 in sJIA patients (P<0.05). In addition, PD-1 expression on CD4 + T cell was negatively associated with the number of involved joints (P<0.05) and PD-L1 on mDC was lower in patients with fever (P<0.01), which could further divide patients into two groups of different manifestations. Our finding displayed decreased CD4 + T cell, increased mDC and reduced PD-1/PD-L1 signal in sJIA PBMC comparing with other JIA subsets, which might be helpful in JIA differential diagnosis and responsible for distinct clinical manifestations via different mechanisms. Copyright © 2018 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Successful treatment of arthritis induced by checkpoint inhibitors with tocilizumab: a case series.

PubMed

Kim, Sang Taek; Tayar, Jean; Trinh, Van Anh; Suarez-Almazor, Maria; Garcia, Salvador; Hwu, Patrick; Johnson, Daniel Hartman; Uemura, Marc; Diab, Adi

2017-12-01

Immune checkpoint inhibitors (ICIs) have significantly improved outcomes for patients with numerous cancers. However, these therapies are associated with immune-related adverse events (irAEs), which are inflammatory side effects potentially affecting any organ. Cases of ICI-induced inflammatory arthritis have also been reported. In general, mild irAEs are treated with corticosteroids, while tumour necrosis factor-α (TNFα) inhibitors are reserved for refractory cases. However, prolonged use of TNFα inhibitor (TNFαi) can induce widespread, significant immunosuppression, which can negatively impact the antitumour efficacy of ICI therapy. Therefore, in clinical scenarios where patients develop severe immunotherapy-induced irAEs, an unmet need exists for alternative therapeutic strategies that are effective and without immune dampening effects. The anti-interleukin (IL)-6 receptor antibody, tocilizumab, is a biological agent Food and Drug Administration approved for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis. Here, we report on three patients who developed severe polyarthritis while receiving ICI therapy and were treated with tocilizumab. All three patients demonstrated significant clinical improvement; one patient maintained a durable antitumour response derived from checkpoint inhibition. These three cases suggest that anti-IL-6 receptor antibody may be an effective alternative to corticosteroids or TNFαi for the treatment of arthritis irAEs. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Inter-trial and test–retest reliability of kinematic and kinetic gait parameters among subjects with adolescent idiopathic scoliosis

PubMed Central

Nadeau, Sylvie; Labelle, Hubert

2007-01-01

Gait analysis is actually used in subjects with scoliosis to determine the change in lower limb parameters after surgery, but the reliability of these parameters still remained unknown. The purpose of this study was to assess the repeatability of traditional gait parameters in subjects with adolescent idiopathic scoliosis (AIS) and to estimate the associated standard error of measurement (SEM). A test–retest design was used to assess the reliability of gait parameters at self-selected and fast speeds. A convenience sample of 20 girls aged from 12 to 17 years, with an idiopathic scoliosis (King classification: types I, II or III; Cobb angle 17–50°) participated in the study. Five good trials were recorded on two occasions. The time-distance, kinematic, and kinetic gait parameters were recorded using foot-switches in combination with a three-dimensional motion analysis system (Optotrak) and Advanced Mechanical Technologies Inc., (AMTI) Watertown, MA, USA; force plates. The coefficients of dependability and SEM derived from the generalizability theory were used to assess the reliability. Inter-trial reliability was good for time-distance, kinematic, and kinetic (absolute and normalized) gait parameters except for the medio-lateral ground reaction force (GRF) component and the ankle dorsiflexor moment (ϕ = 0.60–0.77). Test–retest reliability was higher for the kinetic than for the kinematic parameters. These coefficients ranged from 0.42 to 0.58 for the time-distance parameters; from 0.55 to 0.88 for the angular displacements and from 0.25 to 0.99 for the kinetic parameters. The SEMs were lower than 3.3° for the angular displacements and lower than 8 Nm (0.15 Nm/kg) and 36 W (0.54 W/Kg) for the joint moments and powers regardless of the speed. Several gait parameters are reliable among subjects with AIS and can be used to assess the evolution of the spinal modifications and the impact of treatment on their lower limb gait pattern. PMID:17891424

MRI of the wrist in juvenile idiopathic arthritis: proposal of a paediatric synovitis score by a consensus of an international working group. Results of a multicentre reliability study.

PubMed

Damasio, Maria Beatrice; Malattia, Clara; Tanturri de Horatio, Laura; Mattiuz, Chiara; Pistorio, Angela; Bracaglia, Claudia; Barbuti, Domenico; Boavida, Peter; Juhan, Karen Lambot; Ording, Lil Sophie Mueller; Rosendahl, Karen; Martini, Alberto; Magnano, GianMichele; Tomà, Paolo

2012-09-01

MRI is a sensitive tool for the evaluation of synovitis in juvenile idiopathic arthritis (JIA). The purpose of this study was to introduce a novel MRI-based score for synovitis in children and to examine its inter- and intraobserver variability in a multi-centre study. Wrist MRI was performed in 76 children with JIA. On postcontrast 3-D spoiled gradient-echo and fat-suppressed T2-weighted spin-echo images, joint recesses were scored for the degree of synovial enhancement, effusion and overall inflammation independently by two paediatric radiologists. Total-enhancement and inflammation-synovitis scores were calculated. Interobserver agreement was poor to moderate for enhancement and inflammation in all recesses, except in the radioulnar and radiocarpal joints. Intraobserver agreement was good to excellent. For enhancement and inflammation scores, mean differences (95 % CI) between observers were -1.18 (-4.79 to 2.42) and -2.11 (-6.06 to 1.83). Intraobserver variability (reader 1) was 0 (-1.65 to 1.65) and 0.02 (-1.39 to 1.44). Intraobserver agreement was good. Except for the radioulnar and radiocarpal joints, interobserver agreement was not acceptable. Therefore, the proposed scoring system requires further refinement.

Idiopathic Intracranial Hypertension in Children and Adolescents: An Update.

PubMed

Cleves-Bayon, Catalina

2018-03-01

Idiopathic intracranial hypertension (IIH), previously known as pseudotumor cerebri syndrome (PTC) is a serious neurological disorder that can lead to irreversible visual loss. Predominantly a disorder affecting women in reproductive years, the pediatric population is not spared. In the past few years, the condition has been redefined, due to new accepted values for opening pressure in children and advances in neuroimaging. Emerging techniques in ophthalmology are being increasingly used to monitor disease in these patients. And, although the treatment tools have not changed in several years, important evidence for efficacy for acetazolamide finally came to light in recent years in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). This review article provides an overview on recent advances in diagnosis, evaluation and treatment of IIH. © 2017 American Headache Society.

Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial.

PubMed

McInnes, Iain B; Kavanaugh, Arthur; Gottlieb, Alice B; Puig, Lluís; Rahman, Proton; Ritchlin, Christopher; Brodmerkel, Carrie; Li, Shu; Wang, Yuhua; Mendelsohn, Alan M; Doyle, Mittie K

2013-08-31

Many patients with psoriasis develop psoriatic arthritis, a chronic inflammatory disease that afflicts peripheral synovial, axial, and entheseal structures. The fully human monoclonal antibody ustekinumab is an efficacious treatment for moderate-to-severe plaque psoriasis. We did a randomised, placebo-controlled, phase 3 trial to assess the safety and efficacy of ustekinumab in patients with active psoriatic arthritis. In this phase 3, multicentre, double-blind, placebo-controlled trial at 104 sites in Europe, North America, and Asia-Pacific, adults with active psoriatic arthritis (≥5 tender and ≥5 swollen joints, C-reactive protein ≥3·0 mg/L) were randomly assigned (1:1:1, by dynamic central randomisation based on an algorithm implemented by an interactive voice-web response system) to 45 mg ustekinumab, 90 mg ustekinumab, or placebo at week 0, week 4, and every 12 weeks thereafter. At week 16, patients with less than 5% improvement in both tender and swollen joint counts entered masked early-escape and were given 45 mg ustekinumab (if in the placebo group) or 90 mg ustekinumab (if in the 45 mg group). At week 24, all remaining patients in the placebo group received ustekinumab 45 mg, which they continued at week 28 and every 12 weeks thereafter. Our primary endpoint was 20% or greater improvement in American College of Rheumatology (ACR20) criteria at week 24. This trial is registered with ClinicalTrials.gov (NCT01009086) and EudraCT (2009-012264-14). Between Nov 30, 2009, and March 30, 2011, 615 patients were randomly assigned-206 to placebo, 205 to 45 mg ustekinumab, and 204 to 90 mg ustekinumab. More ustekinumab-treated (87 of 205 [42·4%] in the 45 mg group and 101 of 204 [49·5%] in the 90 mg group) than placebo-treated (47 of 206 [22·8%]) patients achieved ACR20 at week 24 (p<0·0001 for both comparisons); responses were maintained at week 52. At week 16, proportions of patients with adverse events were similar in the ustekinumab and placebo groups

Efficacy of high-dose intravenous immunoglobulins in two patients with idiopathic recurrent pericarditis refractory to previous immunosuppressive treatment.

PubMed

Tona, Francesco; Bellotto, Fabio; Laveder, Francesco; Meneghin, Alessia; Sinagra, Gianfranco; Marcolongo, Renzo

2003-01-01

Although idiopathic acute pericarditis is usually a self-limiting disease, in many patients it may recur over a period of months or years. Even if some evidence seems to suggest the possible role of a deranged immune reactivity in the pathogenesis of idiopathic recurrent pericarditis, the etiology of the disease is still unknown. Furthermore, while some trial data confirm the usefulness of colchicine, its medical treatment is not yet clearly established. We here report the clinical history of 2 patients with idiopathic recurrent pericarditis resistant to prednisone, colchicine and other immunosuppressive drugs, who have been successfully treated with high-dose intravenous immunoglobulins.

Unstimulated salivary flow, pH, proteins and oral health in patients with Juvenile Idiopathic Arthritis.

PubMed

Kobus, Agnieszka; Kierklo, Anna; Zalewska, Anna; Kuźmiuk, Anna; Szajda, Sławomir Dariusz; Ławicki, Sławomir; Bagińska, Joanna

2017-06-02

There have been inconsistent conclusions regarding salivary abnormalities and their effect on oral health of Juvenile Idiopathic Arthritis (JIA) patients. The purpose of the study was to evaluate the flow rate and selected biochemical parameters of unstimulated whole saliva in correlation to oral health in JIA children. Thirty-four JIA patients and 34 age- and sex-matched controls not affected by JIA (C) were divided into two groups: with mixed and permanent dentition. DMFT/dmft, gingival and simplified oral hygiene indices were evaluated. Salivary flow rate, pH, lysozyme, lactoferrin, salivary protein concentrations and peroxidase activity were assessed. The salivary flow rate was significantly lower in the total JIA group (0.41 ml/min) as compared with the C (0.51 ml/min) and in the permanent dentition of JIA children (0.43 ml/min) as compared with the C (0.61 ml/min). A significantly lower pH was observed in total (6.74), mixed (6.7) and permanent (6.76) dentition of JIA groups in comparison to the C (7.25, 7.21, 7.28 respectively). The specific activity of peroxidase was significantly higher in JIA patients (total 112.72 IU/l, mixed dentition 112.98 IU/l, permanent dentition 112.5 IU/l) than in the C group (total 70.03 IU/l, mixed dentition 71.83 IU/l, permanent dentition 68.61 IU/l). The lysozyme concentration in JIA patients (total and permanent dentition groups) was significantly higher than in the C group. There were no significant differences in lactoferrin and salivary protein concentrations. There were no statistically significant differences in oral status between JIA patients and C, respectively: DMFT = 5.71, dmft = 3.73, OHI-S = 0.95, GI = 0.25 and DMFT 5.71, dmft = 3.73, OHI-S = 0.85, GI = 0.24. The specific activity of peroxidase in the unstimulated whole saliva was inversely correlated with the GI index, whereas the salivary lysozyme concentration was inversely correlated with the dmft index in JIA patients. In

The efficacy of the traditional Chinese medicine Juanbi pill combined with methotrexate in active rheumatoid arthritis: study protocol for a randomized controlled trial.

PubMed

Wang, Qiong; Wang, Yi-Ru; Jia, Qing-Yun; Liu, Li; Xu, Chong-Qing; Wang, Xiao-Yun; Yao, Min; Cui, Xue-Jun; Shi, Qi; Wang, Yong-Jun; Liang, Qian-Qian

2018-03-20

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by swelling and painful joints, eventually leading to joint destruction. There is still a lack of effective therapy to treat RA. The Juanbi pill is a Chinese medicine that has been widely used to treat active RA in China for hundreds of years, relieving pain and protecting the affected joints from malformation. However, there is no solid evidence to show the effect of the Juanbi pill on the management of active RA. We will conduct a multicenter, randomized, double-blind, placebo-controlled clinical trial to determine whether the traditional Chinese medicine Juanbi pill could relieve joint pain in RA and protect the joints. A total of 120 patients with active RA will be enrolled and treated with the Juanbi pill or a placebo for 3 months. The primary outcome measures are as follows: rate of in the American College of Rheumatology (ACR)50, change in the 28-joint Disease Activity Score (DAS28) from baseline at beginning of therapy to 3 months, and a change in the van der Heijde modified Sharp score measured from baseline to 12 months. The secondary outcome measures are as follows: rate of change in ACR20, ACR70, Health Assessment Questionnaire-Disability Index (HAQ-DI), and change in score in the Patient Assessment of Arthritis Pain, Patient Global Assessment of Arthritis, and the Athens Insomnia Scale (AIS) from baseline to 2-week, 1-month, 2-month, 3-month, 6-month, and 12-month follow up. In addition, the rate of change (score) in the ACR50 and DAS28 from the baseline to 2-week, 1-month, 2-month, 6-month, and 12-month follow up are also the secondary outcome measures. Although the Juanbi pill has been used in China for many years to treat RA, there is a lack of consensus about its effectiveness. This trial will provide convincing evidence about the effect of Juanbi pill on active RA. ClinicalTrials.gov, NCT02885597 . Registered on 30 August 2016.

A pilot study of yoga as self-care for arthritis in minority communities

PubMed Central

2013-01-01

months. Discussion There are a number of challenges in recruiting and retaining participants from a community clinic serving minority populations. Adopting behaviors that improve well-being and quality of life include those that integrate mental health (mind) and physical health (body). Few studies have examined offering integrative modalities to this population. This pilot was undertaken to quantify measures of feasibility and acceptability that will be useful when evaluating future plans for expanding the study of yoga in urban, minority populations with arthritis. Trial registration ClinicalTrials.gov: NCT01617421 PMID:23548052

Secukinumab in the Treatment of Psoriasis and Psoriatic Arthritis: A Review of the Literature.

PubMed

Abrouk, M; Gandy, J; Nakamura, M; Lee, K; Brodsky, M; Singh, R; Zhu, H; Farahnik, B; Bhutani, T; Koo, J

2017-07-01

While there are several commercially available treatment options for psoriasis and psoriatic arthritis, there remains a large number of individuals who are refractory to current modalities. In the recent past, there has been increasing evidence that interleukin (IL)-17 plays a vital role in the pathophysiology of psoriasis. Preclinical, phase II, and phase III studies of secukinumab (Cosentyx®) targeting IL-17 and its receptor have thus far proved to be promising. We reviewed the results of phase II and phase III clinical trials for secukinumab in the treatment of psoriasis and psoriatic arthritis. Only published studies were considered in the present review. We also performed an English language literature search from January 2003 to September 2015 using PubMed with any of the following key words: (secukinumab OR AIN457) AND (psoriasis OR psoriatic arthritis). In our review of the literature, seven phase III and five phase II clinical trials, as well as open-label extension studies with unpublished findings were found. Results from phase III clinical trials indicated secukinumab to be efficacious and safe for the treatment of psoriasis and psoriatic arthritis according to Psoriasis Area and Severity Index (PASI) and American College of Rheumatology (ACR) scores. The safety profile of this agent was similar across all studies, with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections, headache, and injection site reaction. Secukinumab demonstrates rapid and robust clinical improvement accompanied by a favorable short- term safety profile. The results of the phase III trials continue to reinforce the theory that the IL-17 pathway is an essential target in psoriasis and psoriatic arthritis treatment. Additional extension studies of lower level evidence are needed to further understand the safety profile of the drug.

Arthritis

MedlinePlus

... or have trouble moving around, you might have arthritis. Most kinds of arthritis cause pain and swelling in your joints. Joints ... joint can become severely damaged. Some kinds of arthritis can also cause problems in your organs, such ...

Efficacy of pirfenidone and disease severity of idiopathic pulmonary fibrosis: Extended analysis of phase III trial in Japan.

PubMed

Taguchi, Yoshio; Ebina, Masahito; Hashimoto, Seishu; Ogura, Takashi; Azuma, Arata; Taniguchi, Hiroyuki; Kondoh, Yasuhiro; Suga, Moritaka; Takahashi, Hiroki; Nakata, Koichiro; Sugiyama, Yukihiko; Kudoh, Shoji; Nukiwa, Toshihiro

2015-11-01

A phase III clinical trial of pirfenidone in patients with idiopathic pulmonary fibrosis (IPF) in Japan has revealed that pirfenidone attenuated the decline in vital capacity (VC) and improved progression-free survival (PFS). We conducted an extended analysis of the pirfenidone trial to investigate its efficacy with respect to IPF severity in the trial population. Patients in the phase III trial were stratified by baseline pulmonary functions including %VC predicted, %diffusion capacity for carbon monoxide predicted, and oxygen saturation by pulse oximetry on exertion and were categorized into mild, moderate, and severe groups of functional impairment. The efficacy of pirfenidone for VC and PFS over 52 weeks was compared among the three sub-populations. Of 264 patients, 102 (39%), 90 (34%), and 72 patients (27%) were classified as having mild, moderate, and severe grades of functional impairment, respectively. This classification was associated with arterial oxygen partial pressure at rest and degree of dyspnea at baseline. While pirfenidone attenuated VC decline at all grades of severity, covariance analysis revealed pirfenidone to have better efficacy in the sub-population with mild-grade IPF. Mixed model repeated measures analysis confirmed that pirfenidone markedly attenuated VC decline in patients with mild-grade IPF compared to its effects in patients with moderate or severe IPF. Pirfenidone also improved PFS markedly in patients with mild-grade IPF. This extended analysis suggested that pirfenidone exerted better therapeutic effects in patients with milder IPF. Further analysis with a larger population is needed to confirm these results. Copyright © 2015. Published by Elsevier B.V.

Lumbar scoliosis associated with spinal stenosis in idiopathic and degenerative cases.

PubMed

Le Huec, J C; Cogniet, A; Mazas, S; Faundez, A

2016-10-01

Degenerative de novo scoliosis is commonly present in older adult patients. The degenerative process including disc bulging, facet arthritis, and ligamentum flavum hypertrophy contributes to the appearance of symptoms of spinal stenosis. Idiopathic scoliosis has also degenerative changes that can lead to spinal stenosis. The aetiology, prevalence, biomechanics, classification, symptomatology, and treatment of idiopathic and degenerative lumbar scoliosis in association with spinal stenosis are reviewed. Review study is based on a review of pertinent but non-exhaustive literature of the last 20 years in PubMed in English language. Retrospective analysis of studies focused on all parameters concerning scoliosis associated with stenosis. Very few publications have focused specifically on idiopathic scoliosis and stenosis, and this was before the advent of modern segmental instrumentation. On the other hand, many papers were found for degenerative scoliosis and stenosis with treatment methods based on aetiology of spinal canal stenosis and analysis of global sagittal and frontal parameters. Satisfactory clinical results after operative treatment range from 83 to 96 % but with increased percentage of complications. Recent literature analysed the importance of stabilizing or not the spine after decompression in such situation knowing the increasing risk of instability after facet resection. No prospective randomized studies were found to support short instrumentation. Long instrumentation and fusion to prevent distabilization after decompression were always associated with higher complication rates. Imbalance patients with unsatisfactory compensation capacities were at risk of complications. Operative treatment using newly proposed classification system of lumbar scoliosis with associated canal stenosis is useful. Sagittal balance and rotatory dislocation are the main parameters to analyse to determine the length of fusion.

Idiopathic Intracranial Hypertension (Pseudotumor Cerebri)

MedlinePlus

... Asked Questions Español Condiciones Chinese Conditions Idiopathic Intracranial Hypertension (Pseudotumor Cerebri) En Español Read in Chinese What is idiopathic intracranial hypertension? Idiopathic intracranial hypertension (IIH) is a disorder that ...

Headache in Idiopathic Intracranial Hypertension: Findings From the Idiopathic Intracranial Hypertension Treatment Trial.

PubMed

Friedman, Deborah I; Quiros, Peter A; Subramanian, Prem S; Mejico, Luis J; Gao, Shan; McDermott, Michael; Wall, Michael

2017-09-01

To characterize the phenotype, headache-related disability, medical co-morbidities, use of symptomatic headache medications, and headache response to study interventions in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). Patients with untreated IIH and mild vision loss enrolled in the IIHTT and randomized to acetazolamide (ACZ) and weight loss or placebo (PLB) and weight loss had prospective assessment of headache disability using the Headache Impact Test-6 (HIT-6) questionnaire. Subjects with headache at the baseline visit were assigned a headache phenotype using the International Classification for Headache Disorders version 3 beta (ICHD-3b). Medication overuse was determined using the participants' reported medication use for the preceding month and ICHD-3b thresholds for diagnosing medication overuse headache. We investigated relationships between headache disability and various other clinical characteristics at baseline and at 6 months. Headache was present in 139 (84%) of the 165 enrollees at baseline. The most common headache phenotypes were migraine (52%), tension-type headache (22%), probable migraine (16%), and probable tension-type headache (4%). Fifty-one (37%) participants overused symptomatic medications at baseline, most frequently simple analgesics. A similar amount of improvement in the adjusted mean (± standard error) HIT-6 score occurred in the ACZ (-9.56 ± 1.05) and PLB groups (-9.11 ± 1.14) at 6 months (group difference -0.45, 95% CI -3.50 to 2.60, P = .77). Headache disability did not correlate with any of the studies, variables of interest, which included: the lumbar puncture opening pressure at baseline or at 6 months, body mass index, the amount of weight lost, papilledema grade, perimetric mean deviation, or the use of hormonal contraception. Headache disability was significantly associated with patient-reported quality of life in the physical, mental, and visual domains. Headache was common, of varied

Congruence between Polysomnography Obstructive Sleep Apnea and the Pediatric Sleep Questionnaire: Fatigue and Health-Related Quality of Life in Juvenile Idiopathic Arthritis

PubMed Central

Ward, Teresa M.; Chen, Maida Lynn; Landis, Carol A.; Ringold, Sarah; Beebe, Dean W.; Pike, Kenneth C.; Wallace, Carol A.

2016-01-01

Purpose To examine the congruence between polysomnography obstructive apnea hypopnea index (OAHI) and parent reported obstructive sleep apnea (OSA) symptoms in 6-to-11 year-old children with juvenile idiopathic arthritis (JIA) and controls; and to compare fatigue and quality of life in JIA and control children based on OAHI and OSA symptoms. Methods Sixty-eight children with JIA and 75 controls and a parent participated. Children underwent one night of polysomnography in a sleep laboratory. Parents completed the sleep-related breathing disorders scale - Pediatric Sleep Questionnaire (PSQ), and both children and parents completed the Pediatric Quality of Life Generic Core Scale and the Multidimensional Fatigue scale. Results In JIA, 86% who met the OAHI clinical criteria for OSA (≥ 1.5) were above the PSQ OSA symptom cut-off score with a sensitivity of 0.86 and a specificity of 0.28. In the control group, 63% who met the OAHI clinical criteria for OSA, were above the PSQ OSA symptom cut-off score, with a sensitivity of 0.63 and a specificity of 0.42. All children above both the clinical criteria for OAHI and OSA symptom cut-off score had the most impaired quality of life and greater fatigue compared to those below both the clinical criteria for OAHI and the OSA symptom cut-off score. Conclusion Children who meet clinical criteria for OSA and also scored high on a parent reported screening tool for OSA symptoms had the most impaired quality of life and more fatigue. The PSQ has potential to identify children at risk for OSA. PMID:27987106

Genome-scale case-control analysis of CD4+ T-cell DNA methylation in juvenile idiopathic arthritis reveals potential targets involved in disease.

PubMed

Ellis, Justine A; Munro, Jane E; Chavez, Raul A; Gordon, Lavinia; Joo, Jihoon E; Akikusa, Jonathan D; Allen, Roger C; Ponsonby, Anne-Louise; Craig, Jeffrey M; Saffery, Richard

2012-11-13

Juvenile Idiopathic Arthritis (JIA) is a complex autoimmune rheumatic disease of largely unknown cause. Evidence is growing that epigenetic variation, particularly DNA methylation, is associated with autoimmune disease. However, nothing is currently known about the potential role of aberrant DNA methylation in JIA. As a first step to addressing this knowledge gap, we have profiled DNA methylation in purified CD4+ T cells from JIA subjects and controls. Genomic DNA was isolated from peripheral blood CD4+ T cells from 14 oligoarticular and polyarticular JIA cases with active disease, and healthy age- and sex-matched controls. Genome-scale methylation analysis was carried out using the Illumina Infinium HumanMethylation27 BeadChip. Methylation data at >25,000 CpGs was compared in a case-control study design. Methylation levels were significantly different (FDR adjusted p<0.1) at 145 loci. Removal of four samples exposed to methotrexate had a striking impact on the outcome of the analysis, reducing the number of differentially methylated loci to 11. The methotrexate-naive analysis identified reduced methylation at the gene encoding the pro-inflammatory cytokine IL32, which was subsequently replicated using a second analysis platform and a second set of case-control pairs. Our data suggests that differential T cell DNA methylation may be a feature of JIA, and that reduced methylation at IL32 is associated with this disease. Further work in larger prospective and longitudinal sample collections is required to confirm these findings, assess whether the identified differences are causal or consequential of disease, and further investigate the epigenetic modifying properties of therapeutic regimens.

The therapeutic effect of probiotics on rheumatoid arthritis: a systematic review and meta-analysis of randomized control trials.

PubMed

Mohammed, Abdelrahman Tarek; Khattab, Mohammed; Ahmed, Ali Mahmoud; Turk, Tarek; Sakr, Nora; M Khalil, Adham; Abdelhalim, Mohamed; Sawaf, Bisher; Hirayama, Kenji; Huy, Nguyen Tien

2017-12-01

Rheumatoid arthritis is an autoimmune disease in which probiotics appears to have an immune modulating action along with decreased inflammatory process. Therefore, we aim to investigate the efficacy of probiotics as an adjuvant therapy for rheumatoid arthritis. A comprehensive literature search was performed using nine databases including PubMed and Web of Science. Interesting data was extracted and meta-analyzed. We assessed the risk of bias using Cochrane Collaboration's tool. The protocol was registered in PROSPERO (CRD 42016036769). We found nine studies involving 361 patients who met our eligibility criteria. Our meta-analysis indicated that pro-inflammatory cytokine IL-6 was significantly lower in the probiotics compared with the placebo group (standardized mean difference = - 0.708; 95% confidence interval (CI) - 1.370 to 0.047, P = 0.036). However, there was no difference between probiotics and placebo in disease activity score (mean difference 0.023; 95% CI - 0.584 to 0.631, P = 0.940). Probiotics lowered pro-inflammatory cytokines IL-6 in RA; however, its clinical effect is still unclear. Hence, many high-quality randomized controlled trials (RCTs) are still needed to prove this effect.

Physical therapy for Bell s palsy (idiopathic facial paralysis).

PubMed

Teixeira, Lázaro Juliano; Soares, Bernardo Garcia de Oliveira; Vieira, Vanessa Pedrosa; Prado, Gilmar F

2008-07-16

Bell's palsy (idiopathic facial paralysis) is commonly treated by physical therapy services with various therapeutic strategies and devices. There are many questions about their efficacy and effectiveness. To evaluate the efficacy of physical therapies on the outcome of Bell's palsy. We searched the Cochrane Neuromuscular Disease Group Trials Register (February 2008), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2007), MEDLINE (January 1966 to February 2008), EMBASE (January 1980 to February 2008), LILACS (January 1982 to February 2008), PEDro (from 1929 to February 2008), and CINAHL (January 1982 to February 2008). We selected randomised or quasi-randomised controlled trials involving any physical therapy. We included participants of any age with a diagnosis of Bell's palsy and all degrees of severity. The outcome measures were: incomplete recovery six months after randomisation, motor synkinesis, crocodile tears or facial spasm six months after onset, incomplete recovery after one year and adverse effects attributable to the intervention. Titles and abstracts identified from the register were scrutinized. The assessment of methodological quality took into account secure method of randomisation, allocation concealment, observer blinding, patient blinding, differences at baseline of the experimental groups, and completeness of follow-up. Data were extracted using a specially constructed data extraction form. Separate subgroup analyses of participants with more and less severe disability were undertaken. The search identified 45 potentially relevant articles. Six studies met the inclusion criteria. Three trials studied the efficacy of electrostimulation (294 participants) and three exercises (253 participants). Neither treatment produced significantly more improvement than the control treatment or no treatment. There was limited evidence that improvement began earlier in the exercise group. There is no evidence of significant

Total pubertal growth in patients with juvenile idiopathic arthritis treated with growth hormone: analysis of a single center.

PubMed

Bechtold, S; Beyerlein, A; Ripperger, P; Roeb, J; Dalla Pozza, R; Häfner, R; Haas, J P; Schmidt, H

2012-10-01

Growth failure is a permanent sequelae in juvenile idiopathic arthritis (JIA). The aim of the study was to compare pubertal growth in control and growth hormone (GH) treated JIA subjects. 64 children with JIA at a mean age of 10.38 ± 2.80 years were enrolled and followed until final height (measured in standard deviation (SD) scores). 39 children (20 m) received GH therapy and 24 (9 m) served as controls. GH dose was 0.33 mg/kg/week. Linear regression analysis was performed to identify factors influencing total pubertal growth. Mean total pubertal growth was 21.1 ± 1.3 cm (mean ± SD) in GH treated JIA patients and 13.8 ± 1.5 cm in controls. Final height was significantly higher with GH treatment (-1.67 ± 1.20 SD) compared to controls (-3.20 ± 1.84 SD). Linear regression model identified age at onset of puberty (ß=-4.2,CI: -5.9, -2.6 in controls and ß=-2.3,CI: -3.6, -1.1 in GH treated) as the main factor for total pubertal growth. Final height SDS was determined by the difference to target height at onset of puberty (ß=-0.59;CI: -0.80, -0.37 in controls and ß=-0.30,CI: -0.52, -0.08 in GH treated), age at onset of puberty (ß=0.47;CI:0.02,0.93 in controls and 0.23;CI: -0.00,0.46 in GH treated) and height gain during puberty (ß=0.13;CI:0.05,0.21 in controls and ß=0.11;CI:0.07,0.16 in GH treated). Total pubertal growth in JIA patients treated with GH was increased by a factor of 1.5 greater in comparison to controls leading to a significantly better final height. To maximize final height GH treatment should be initiated early to reduce the height deficit at onset of puberty. Copyright © 2012 Elsevier Ltd. All rights reserved.

78 FR 66029 - National Institute of Arthritis and Musculoskeletal and Skin Diseases Amended; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases Amended; Notice of Meeting Notice is hereby given of a change in the meeting of the Arthritis and Musculoskeletal and Skin Diseases Clinical Trials Review...

Leflunomide is associated with a higher flare rate compared to methotrexate in the treatment of chronic uveitis in juvenile idiopathic arthritis.

PubMed

Bichler, J; Benseler, S M; Krumrey-Langkammerer, M; Haas, J-P; Hügle, B

2015-01-01

Chronic anterior uveitis is a serious complication of juvenile idiopathic arthritis (JIA); disease flares are highly associated with loss of vision. Leflunomide (LEF) is used successfully for JIA joint disease but its effectiveness in uveitis has not been determined. The aim of this study was to determine whether LEF improves flare rates of uveitis in JIA patients compared to preceding methotrexate (MTX) therapy. A single-centre retrospective study of consecutive children with JIA and chronic anterior uveitis was performed. All children initially received MTX and were then switched to LEF. Demographic, clinical, and laboratory data, dose and duration of MTX and LEF therapy, concomitant medications and rate of anterior uveitis flares, as determined by an expert ophthalmologist, were obtained. Flare rates were compared using a generalized linear mixed model with a negative binomial distribution. A total of 15 children were included (80% females, all antinuclear antibody positive). The median duration of MTX therapy was 51 (range 26-167) months; LEF was given for a median of 12 (range 4-47) months. Anti-tumour necrosis factor (anti-TNF-α) co-medication was given to four children while on MTX. By contrast, LEF was combined with anti-TNF-α treatment in six children. On MTX, JIA patients showed a uveitis flare rate of 0.0247 flares/month, while LEF treatment was associated with a significantly higher flare rate of 0.0607 flares/month (p = 0.008). Children with JIA had significantly more uveitis flares on LEF compared to MTX despite receiving anti-TNF-α co-medication more frequently. Therefore, LEF may need to be considered less effective in controlling chronic anterior uveitis.

Arthritis as presenting manifestation of acute lymphoblastic leukaemia in children.

PubMed

Brix, Ninna; Rosthøj, Steen; Herlin, Troels; Hasle, Henrik

2015-09-01

At disease onset, children with acute lymphoblastic leukaemia (ALL) may present with arthralgia or even signs of arthritis. This might cause misdiagnosis and thereby lead to prolonged diagnostic delay. The present study aimed to identify children with ALL with joint involvement and to compare their characteristics and outcome with children with ALL without joint involvement. Case records of 286 children diagnosed with ALL between 1992 and 2013 were reviewed and analysed in this retrospective, descriptive study. Fifty-three (18.5%) children with ALL presented with localised joint pain, and half of them had objective signs of arthritis. The mean number of joints involved was 2.5, most frequently presenting as asymmetric oligoarthritis. The suspected misdiagnosis were reactive arthritis (19/53), osteomyelitis (9/53) and juvenile idiopathic arthritis (8/53). Children with joint involvement had less objective signs of haematological disease. Cytopenia was absent in 24% in children with joint involvement (vs 8% without, p=0.001), 50% had only one cell line affected (vs 21%, p=0.0005) and 44% had no organomegaly (vs 29%, p=0.05). Median diagnostic delay was 4 vs 2 weeks. The 5-year event-free and overall survival was superior for children with joint involvement: 94% vs 87% (p=0.049), and 96% vs 83% (p=0.044). ALL with joint involvement is a frequent finding (18.5%). The clinical signs of leukaemia are less prominent, but non-articular pain should alert the clinician of a possible diagnosis of leukaemia. The overall and event-free survivals were superior compared with the children without joint involvement. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Psoriatic arthritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gerber, L.H.; Espinoza, L.R.

1985-01-01

This book contains 11 chapters. Some of the titles are: The history and epidemiologic definition of psoriatic arthritis as a distinct entity; Psoriatic arthritis: Further epidemiologic and genetic considerations; The radiologic features of psoriatic arthritis; and Laboratory findings and pathology of psoriatic arthritis.

IL-6 blockade in systemic juvenile idiopathic arthritis - achievement of inactive disease and remission (data from the German AID-registry).

PubMed

Bielak, M; Husmann, E; Weyandt, N; Haas, J-P; Hügle, B; Horneff, G; Neudorf, U; Lutz, T; Lilienthal, E; Kallinich, T; Tenbrock, K; Berendes, R; Niehues, T; Wittkowski, H; Weißbarth-Riedel, E; Heubner, G; Oommen, P; Klotsche, J; Foell, Dirk; Lainka, E

2018-04-05

Systemic juvenile idiopathic arthritis (sJIA) is a complex disease with an autoinflammatory component of unknown etiology related to the innate immune system. A major role in the pathogenesis has been ascribed to proinflammatory cytokines like interleukin-6 (IL-6), and effective drugs inhibiting their signaling are being developed. This study evaluates sJIA patients treated with the IL-6 inhibitor tocilizumab (TCZ) concerning clinical response rate, disease course and adverse effects in a real-life clinical setting. In 2009 a clinical and research consortium was established, including an online registry for autoinflammatory diseases (AID) ( https://aid-register.de ). Data for this retrospective TCZ study were documented by 13 centers. From 7/2009 to 4/2014, 200 patients with sJIA were recorded in the AID-registry. Out of these, 46 (19 m, 27 f, age 1-18 years) received therapy with TCZ. Long term treatment (median 23 months) has been documented in 24/46 patients who were evaluated according to Wallace criteria (active disease 6/24, inactive disease 5/24, remission 13/24 cases). Under observation co-medication were used in 40/46 cases. Adverse events were reported in 11/46 patients. The clinical response rate (no clinical manifestation, no increased inflammation parameters) within the first 12 weeks of treatment was calculated to be 35%. Out of 200 sJIA children reported in the German AID-registry, 46 were treated with TCZ, showing a clinical response rate of 35% during the first 12 weeks, and inactive disease and/or remission under medication in 75% after one year. Adverse events were seen in 24% and severe adverse events in 4%. The AID-Registry is funded by the BMBF (01GM08104, 01GM1112D, 01GM1512D).

Vocal cord paralysis: What matters between idiopathic and non-idiopathic cases?

PubMed

Özbal Koç, Ayça Eltaf; Türkoğlu, Seda Babakurban; Erol, Ozan; Erbek, Selim

2016-01-01

This study aims to evaluate the demographic and clinical characteristics of patients with idiopathic and non-idiopathic vocal cord paralysis (VCP). This retrospective cohort was performed on data extracted from medical files of 92 consecutive patients (43 males, 49 females; median age 52.1±23.1 years; min. 1 - max. 87) with VCP diagnosed in the otorhinolaryngology department between April 2012 and December 2015. Diagnoses associated with VCP, side of involvement (right, left or bilateral) and previous medical histories were noted and compared between patients with idiopathic and non-idiopathic VCP. Vocal cord paralysis occurred on the left side (n=56, 60.9%), right side (n=28, 30.4%) or bilaterally (n=8, 8.7%). A clinical entity related with VCP was identified in 63 patients (68.5%), while 29 (31.5%) patients had idiopathic VCP. Most common etiologies for VCP were thyroid surgery (n=32, 34.8%), cardiovascular surgery (n=9, 9.8%), lung cancer (n=6, 6.5%) and cardiac anomalies (n=4, 4.3%), respectively. Patients with idiopathic VCP were significantly older (p<0.001), while gender distribution (p=0.121) and side of involvement (p=0.340) did not differ between two groups. Vocal cord paralysis is a relatively common clinical entity with substantial rate of morbidity. Identification of the underlying etiology and awareness on the clinical characteristics are keystones for foreseeing complications and determining the appropriate therapeutic modality.

Rheumatoid Arthritis

MedlinePlus

... Rheumatoid Arthritis English Español 繁體中文 한국어 tiếng Việt Rheumatoid Arthritis Basics In-Depth Download Download EPUB Download PDF What is it? Points To Remember About Rheumatoid Arthritis Rheumatoid arthritis is a disease that causes pain, ...

76 FR 65737 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-24

... Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the... Arthritis and Musculoskeletal and Skin Diseases Special Emphasis Panel, Clinical Trials Grant Review. Date..., Musculoskeletal and Skin Diseases, 6701 Democracy Blvd, Plaza Suite 800, Bethesda, MD 20817, 301-594-4952...

75 FR 70679 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-18

... Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the... Institute of Arthritis and Musculoskeletal and Skin Diseases Special Emphasis Panel, Clinical Trials Review... Skin Diseases, National Institutes of Health, 6701 Democracy Blvd, Room 824, MSC 4872, Bethesda, MD...

[Garlic effectiveness in rheumatoid arthritis].

PubMed

Denisov, L N; Andrianova, I V; Timofeeva, S S

1999-01-01

To perform of clinical trial of alisate--a garlic preparation produced in Russia. An open controlled trial of alisate enrolled 30 patients with rheumatoid arthritis (RA). 15 patients with RA of varying clinical form, stage and activity were given alisate in a dose 300 mg (1 tablet) twice a day for 4-6 weeks. 15 control RA patients received conventional antirheumatic therapy. The alisate group achieved a good and partial response in 86.5% of cases. The drug was well tolerated and had no side effects. In control group, some parameters changed for the worse. Alisate can be recommended for treatment of RA patients in combined and monotherapy.

Two-year Efficacy and Safety of Etanercept in Pediatric Patients with Extended Oligoarthritis, Enthesitis-related Arthritis, or Psoriatic Arthritis.

PubMed

Constantin, Tamas; Foeldvari, Ivan; Vojinovic, Jelena; Horneff, Gerd; Burgos-Vargas, Ruben; Nikishina, Irina; Akikusa, Jonathan D; Avcin, Tadej; Chaitow, Jeffrey; Koskova, Elena; Lauwerys, Bernard R; Calvo Penades, Inmaculada; Flato, Berit; Gamir, Maria Luz; Huppertz, Hans-Iko; Jaller Raad, Juan Jose; Jarosova, Katerina; Anton, Jordi; Macku, Marie; Otero Escalante, William J; Rutkowska-Sak, Lidia; Trauzeddel, Ralf; Velez-Sanchez, Patricia J; Wouters, Carine; Wajdula, Joseph; Zang, Chuanbo; Bukowski, Jack; Woodworth, Deborah; Vlahos, Bonnie; Martini, Alberto; Ruperto, Nicolino

2016-04-01

The main objective was to determine the 2-year clinical benefit and safety of etanercept (ETN) in children with the juvenile idiopathic arthritis (JIA) categories of extended oligoarthritis (eoJIA), enthesitis-related arthritis (ERA), or psoriatic arthritis (PsA). CLIPPER was a 96-week, phase IIIb, open-label, multicenter study. Patients with eoJIA, ERA, or PsA received ETN 0.8 mg/kg once weekly (50 mg max) for up to 96 weeks. The proportions of patients reaching the JIA American College of Rheumatology (ACR) 30/50/70/90/100 and inactive disease responses at Week 96 were calculated. Adverse events (AE) were collected throughout the study (intention-to-treat sample). There were 127 patients (eoJIA n = 60, ERA n = 38, PsA n = 29) who received ≥ 1 dose of ETN. The mean disease duration was 31.6 (eoJIA), 23.0 (ERA), and 21.8 (PsA) months. At Week 96, JIA ACR 30/50/70/90/100/inactive disease responses (95% CI) were achieved by 84.3% (76.7, 90.1), 83.5% (75.8, 89.5), 78.7% (70.6, 85.5), 55.1% (46.0, 63.9), 45.7% (36.8, 54.7), and 27.6% (20.0, 36.2) of patients, respectively. The most common AE (no. events, events per 100 patient-yrs) overall were headache (23, 10.7), pyrexia (12, 5.6), and diarrhea (10, 4.6). The most common infections were upper respiratory tract infection (83, 38.6), pharyngitis (50, 23.2), gastroenteritis (22, 10.2), bronchitis (19, 8.8), and rhinitis (17, 7.9). No cases of malignancy, active tuberculosis, demyelinating disorders, or death were reported. Over 96 weeks of therapy, ETN demonstrated sustained efficacy at treating the clinical symptoms of all 3 JIA categories, with no major safety issues.

Influence of periodontal treatment on rheumatoid arthritis: a systematic review and meta-analysis.

PubMed

Calderaro, Débora Cerqueira; Corrêa, Jôice Dias; Ferreira, Gilda Aparecida; Barbosa, Izabela Guimarães; Martins, Carolina Castro; Silva, Tarcília Aparecida; Teixeira, Antônio Lúcio

To evaluate the influence of periodontal treatment on rheumatoid arthritis activity. MEDLINE/PUBMED, The Cochrane Library, Clinical Trials, SciELO and LILACS were searched for studies published until December 2014. Included articles were: prospective studies; including patients older than 18 years, diagnosed with periodontitis and rheumatoid arthritis submitted to non-surgical periodontal treatment; with a control group receiving no periodontal treatment; with outcomes including at least one marker of rheumatoid arthritis activity. Methodological quality of the studies was assessed using PEDro scale. Quantitative data were pooled in statistical meta-analysis using Review Manager 5. Four articles were included. Non-surgical periodontal treatment was associated with a significant reduction of DAS28 (OR: -1.18; 95% CI: -1.43, -0.93; p<0.00001). Erythrocyte sedimentation rate, C-reactive protein, patient's assessment of rheumatoid activity using visual analogical scale, tender and swollen joint counts showed a trend toward reduction (not statistically significant). The reduction of DAS 28 in patients with rheumatoid arthritis after periodontal treatment suggests that the improvement of periodontal condition is beneficial to these patients. Further randomized controlled clinical trials are necessary to confirm this finding. Copyright © 2016. Published by Elsevier Editora Ltda.

Influence of periodontal treatment on rheumatoid arthritis: a systematic review and meta-analysis.

PubMed

Calderaro, Débora Cerqueira; Corrêa, Jôice Dias; Ferreira, Gilda Aparecida; Barbosa, Izabela Guimarães; Martins, Carolina Castro; Silva, Tarcília Aparecida; Teixeira, Antônio Lúcio

2016-11-26

To evaluate the influence of periodontal treatment on rheumatoid arthritis activity. MEDLINE/PUBMED, The Cochrane Library, Clinical Trials, SciELO and LILACS were searched for studies published until December 2014. Included articles were: prospective studies; including patients older than 18 years, diagnosed with periodontitis and rheumatoid arthritis submitted to non-surgical periodontal treatment; with a control group receiving no periodontal treatment; with outcomes including at least one marker of rheumatoid arthritis activity. Methodological quality of the studies was assessed using PEDro scale. Quantitative data were pooled in statistical meta-analysis using Review Manager 5. Four articles were included. Non-surgical periodontal treatment was associated with a significant reduction of DAS28 (OR: -1.18; 95% CI: -1.43, -0.93; p <0.00001). Erythrocyte sedimentation rate, C-reactive protein, patient's assessment of rheumatoid activity using visual analogical scale, tender and swollen joint counts showed a trend towards reduction (not statistically significant). The reduction of DAS 28 in patients with rheumatoid arthritis after periodontal treatment suggests that the improvement of periodontal condition is beneficial to these patients. Further randomized controlled clinical trials are necessary to confirm this finding. Copyright © 2016. Published by Elsevier Editora Ltda.

Baseline OCT Measurements in the Idiopathic Intracranial Hypertension Treatment Trial, Part I: Quality Control, Comparisons, and Variability

PubMed Central

2014-01-01

Purpose. Optical coherence tomography (OCT) has been used to investigate papilledema in single-site, mostly retrospective studies. We investigated whether spectral-domain OCT (SD-OCT), which provides thickness and volume measurements of the optic nerve head and retina, could reliably demonstrate structural changes due to papilledema in a prospective multisite clinical trial setting. Methods. At entry, 126 subjects in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) with mild visual field loss had optic disc and macular scans, using the Cirrus SD-OCT. Images were analyzed by using the proprietary commercial and custom 3D-segmentation algorithms to calculate retinal nerve fiber layer (RNFL), total retinal thickness (TRT), optic nerve head volume (ONHV), and retinal ganglion cell layer (GCL) thickness. We evaluated variability, with interocular comparison and correlation between results for both methods. Results. The average RNFL thickness > 95% of normal controls in 90% of eyes and the RNFL, TRT, ONH height, and ONHV showed strong (r > 0.8) correlations for interocular comparisons. Variability for repeated testing of OCT parameters was low for both methods and intraclass correlations > 0.9 except for the proprietary GCL thickness. The proprietary algorithm–derived RNFL, TRT, and GCL thickness measurements had failure rates of 10%, 16%, and 20% for all eyes respectively, which were uncommon with 3D-segmentation–derived measurements. Only 7% of eyes had GCL thinning that was less than fifth percentile of normal age-matched control eyes by both methods. Conclusions. Spectral-domain OCT provides reliable continuous variables and quantified assessment of structural alterations due to papilledema. (ClinicalTrials.gov number, NCT01003639.) PMID:25370510

Treatment options in idiopathic subglottic stenosis: protocol for a prospective international multicentre pragmatic trial

PubMed Central

Shyr, Yu; Berry, Lynne; Hillel, Alexander T; Ekbom, Dale C; Edell, Eric S; Kasperbauer, Jan L; Lott, David G; Donovan, Donald T; Garrett, C. Gaelyn; Sandhu, Guri; Daniero, James J; Netterville, James L; Schindler, Josh S; Smith, Marshall E; Bryson, Paul C; Lorenz, Robert R; Francis, David O

2018-01-01

Introduction Idiopathic subglottic stenosis (iSGS) is an unexplained progressive obstruction of the upper airway that occurs almost exclusively in adult, Caucasian women. The disease is characterised by mucosal inflammation and localised fibrosis resulting in life-threatening blockage of the upper airway. Because of high recurrence rates, patients with iSGS will frequently require multiple procedures following their initial diagnosis. Both the disease and its therapies profoundly affect patients’ ability to breathe, communicate and swallow. A variety of treatments have been advanced to manage this condition. However, comparative data on effectiveness and side effects of the unique approaches have never been systematically evaluated. This study will create an international, multi-institutional prospective cohort of patients with iSGS. It will compare three surgical approaches to determine how well the most commonly used treatments in iSGS ‘work’ and what quality of life (QOL) trade-offs are associated with each approach. Methods and analysis A prospective pragmatic trial comparing the ‘Standard of Care’ for iSGS at multiple international institutions. Patients with a diagnosis of iSGS without clinical or laboratory evidence of vasculitis or a history of endotracheal intubation 2 years prior to symptom onset will be included in the study. Prospective evaluation of disease recurrence requiring operative intervention, validated patient-reported outcome (PRO) measures as well as patient-generated health data (mobile peak flow recordings and daily steps taken) will be longitudinally tracked for 36 months. The primary endpoint is treatment effectiveness defined as time to recurrent operative procedure. Secondary endpoints relate to treatment side effects and include PRO measures in voice, swallowing, breathing and global QOL as well as patient-generated health data. Ethics and dissemination This protocol was approved by the local IRB Committee of the

The French version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).

PubMed

Quartier, Pierre; Hofer, Michael; Wouters, Carine; Truong, Thi Thanh Thao; Duong, Ngoc-Phoi; Agbo-Kpati, Kokou-Placide; Uettwiller, Florence; Melki, Isabelle; Mouy, Richard; Bader-Meunier, Brigitte; Consolaro, Alessandro; Bovis, Francesca; Ruperto, Nicolino

2018-04-01

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the French language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations and construct validity (convergent and discriminant validity). A total of 100 JIA patients (23% systemic, 45% oligoarticular, 20% RF negative polyarthritis, 12% other categories) and 122 healthy children, were enrolled at the paediatric rheumatology centre of the Necker Children's Hospital in Paris. Notably, none of the enrolled JIA patients is affected with psoriatic arthritis. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the French version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

Education and employment in patients with juvenile idiopathic arthritis - a standardized comparison to the German general population.

PubMed

Schlichtiger, Jenny; Haas, Johannes-Peter; Barth, Swaantje; Bisdorff, Betty; Hager, Lisa; Michels, Hartmut; Hügle, Boris; Radon, Katja

2017-05-22

Although several studies show that JIA-patients have significantly lower employment rates than the general population, the research on educational and occupational attainments in patients with juvenile idiopathic arthritis (JIA) remain conflicting most likely due to small sample sizes. Therefore, aim of this study is to compare the educational achievements and employment status of 3698 JIA-patients with the German general population (GGP). "SEPIA" was a large cross-sectional study on the current status of a historic cohort of JIA-patients treated in a single center between 1952 and 2010. For the analyses of education and employment a sub-cohort was extracted, including only adult cases with a confirmed diagnosis of JIA (N = 2696). Participants were asked to fill out a standardized written questionnaire on education and employment. Outcome measures (education/unemployment) were directly standardized to the GGP using data obtained from the National Educational Panel Study 2013 (N = 11,728) and the German Unemployment Statistics 2012 of the Federal Statistical Office (N = 42,791,000). After age- and sex-standardization, 3% (95% Confidence Interval 1.9 to 4.1%) more of the JIA-patients (26%) than of the GGP (23%) had only reached primary education. In contrast, parents of JIA-patients had similar levels of education as parents in the GGP. With a standardized difference of 0.2% (95% CI: 0.16 to 0.19%), the unemployment rate in JIA-patients was slightly, but not significantly higher than in the GGP. Stratifying for disease duration and the current treatment status, differences were confirmed for persons diagnosed before 2001, whilst for patients diagnosed after 2000, differences were found only in JIA-patients with ongoing disease. Medium and high educational achievements did not differ statistically significant between JIA patients and the GPP. Educational achievements in German JIA-patients are significantly lower than in the GGP. Furthermore we were able to

Pirfenidone Reduces Respiratory-related Hospitalizations in Idiopathic Pulmonary Fibrosis.

PubMed

Ley, Brett; Swigris, Jeffrey; Day, Bann-Mo; Stauffer, John L; Raimundo, Karina; Chou, Willis; Collard, Harold R

2017-09-15

Respiratory-related hospitalizations of patients with idiopathic pulmonary fibrosis (IPF) are more frequent than those for acute IPF exacerbations and are associated with poor outcomes. To compare the risk of nonelective hospitalization by type (all-cause, respiratory related, and non-respiratory related) and death after hospitalization with use of pirfenidone versus placebo over 52 weeks using data derived from three phase III IPF clinical trials. Individual patient data was pooled from three phase III randomized, placebo-controlled studies of pirfenidone for IPF (the two CAPACITY [Clinical Studies Assessing Pirfenidone in IPF: Research of Efficacy and Safety Outcomes] trials and the ASCEND [Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis] trial), including all patients randomized to pirfenidone 2,403 mg/d (n = 623) or placebo (n = 624). The risk of hospitalization over 52 weeks was compared using standard time-to-event methods. Among those hospitalized, the risk of death after hospitalization was compared with adjustment for treatment group propensity. A total of 1,247 patients (692 from the CAPACITY trials and 555 from the ASCEND trial) were included in the pooled analysis. Pirfenidone was associated with lower risk of respiratory-related hospitalization than placebo (7% vs. 12%; hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.36-0.77; P = 0.001), but all-cause (HR, 0.91; 95% CI, 0.70-1.19; P = 0.528) or non-respiratory-related hospitalization (HR, 1.32; 95% CI, 0.92-1.88; P = 0.145) was not. Among those hospitalized for any reason, treatment with pirfenidone was associated with lower risk of death after hospitalization up to 52 weeks after randomization, but this association was no longer significant with longer follow-up. In a pooled analysis of three phase III IPF clinical trials, patients receiving pirfenidone had a lower risk of nonelective respiratory-related hospitalization over the

The role of helplessness, outcome expectation for exercise and literacy in predicting disability and symptoms in older adults with arthritis.

PubMed

Bhat, Anita A; DeWalt, Darren A; Zimmer, Catherine R; Fried, Bruce J; Callahan, Leigh F

2010-10-01

To examine the effect of outcome expectation for exercise (OEE), helplessness, and literacy on arthritis outcomes in 2 community-based lifestyle randomized controlled trials (RCTs) conducted in urban and rural communities with older adults with arthritis. Data from 391 participants in 2 RCTs were combined to examine associations of 2 psychosocial variables: helplessness and OEE, and literacy with arthritis outcomes. Arthritis outcomes namely, the Health Assessment Questionnaire-Disability Index (HAQ-DI) and arthritis symptoms pain, fatigue and stiffness Visual Analogue Scales (VAS), were measured at baseline and at the end of the interventions. Complete baseline and post-intervention data were analyzed using STATA version 9. Disability after intervention was not predicted by helplessness, literacy, or OEE in the adjusted model. Arthritis symptoms after the intervention were all significantly predicted by helplessness at various magnitudes in adjusted models, but OEE and literacy were not significant predictors. When literacy, helplessness, and OEE were examined as predictors of arthritis outcomes in intervention trials, they did not predict disability. However, helplessness predicted symptoms of pain, fatigue, and stiffness, but literacy did not predict symptoms. Future sustainable interventions may include self-management components that address decreasing helplessness to improve arthritis outcomes. (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Genome-wide association study of response to methotrexate in early rheumatoid arthritis patients.

PubMed

Taylor, John C; Bongartz, Tim; Massey, Jonathan; Mifsud, Borbala; Spiliopoulou, Athina; Scott, Ian C; Wang, Jianmei; Morgan, Michael; Plant, Darren; Colombo, Marco; Orchard, Peter; Twigg, Sarah; McInnes, Iain B; Porter, Duncan; Freeston, Jane E; Nam, Jackie L; Cordell, Heather J; Isaacs, John D; Strathdee, Jenna L; Arnett, Donna; de Hair, Maria J H; Tak, Paul P; Aslibekyan, Stella; van Vollenhoven, Ronald F; Padyukov, Leonid; Bridges, S Louis; Pitzalis, Costantino; Cope, Andrew P; Verstappen, Suzanne M M; Emery, Paul; Barnes, Michael R; Agakov, Felix; McKeigue, Paul; Mushiroda, Taisei; Kubo, Michiaki; Weinshilboum, Richard; Barton, Anne; Morgan, Ann W; Barrett, Jennifer H

2018-05-25

Methotrexate (MTX) monotherapy is a common first treatment for rheumatoid arthritis (RA), but many patients do not respond adequately. In order to identify genetic predictors of response, we have combined data from two consortia to carry out a genome-wide study of response to MTX in 1424 early RA patients of European ancestry. Clinical endpoints were change from baseline to 6 months after starting treatment in swollen 28-joint count, tender 28-joint count, C-reactive protein and the overall 3-component disease activity score (DAS28). No single nucleotide polymorphism (SNP) reached genome-wide statistical significance for any outcome measure. The strongest evidence for association was with rs168201 in NRG3 (p = 10 -7 for change in DAS28). Some support was also seen for association with ZMIZ1, previously highlighted in a study of response to MTX in juvenile idiopathic arthritis. Follow-up in two smaller cohorts of 429 and 177 RA patients did not support these findings, although these cohorts were more heterogeneous.

A double-blind, randomized controlled trial to compare the effect of biannual peripheral magnetic resonance imaging, radiography and standard of care disease progression monitoring on pharmacotherapeutic escalation in rheumatoid and undifferentiated inflammatory arthritis: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Permanent joint damage is a major consequence of rheumatoid arthritis (RA), the most common and destructive form of inflammatory arthritis. In aggressive disease, joint damage can occur within 6 months from symptom onset. Early, intensive treatment with conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) can delay the onset and progression of joint damage. The primary objective of the study is to investigate the value of magnetic resonance imaging (MRI) or radiography (X-ray) over standard of care as tools to guide DMARD treatment decision-making by rheumatologists for the care of RA. Methods A double-blind, randomized controlled trial has been designed. Rheumatoid and undifferentiated inflammatory arthritis patients will undergo an MRI and X-ray assessment every 6 months. Baseline adaptive randomization will be used to allocate participants to MRI, X-ray, or sham-intervention groups on a background of standard of care. Prognostic markers, treating physician, and baseline DMARD therapy will be used as intervention allocation parameters. The outcome measures in rheumatology RA MRI score and the van der Heijde-modified Sharp score will be used to evaluate the MRI and X-ray images, respectively. Radiologists will score anonymized images for all patients regardless of intervention allocation. Disease progression will be determined based on the study-specific, inter-rater smallest detectable difference. Allocation-dependent, intervention-concealed reports of positive or negative disease progression will be reported to the treating rheumatologist. Negative reports will be delivered for the sham-intervention group. Study-based radiology clinical reports will be provided to the treating rheumatologists for extra-study X-ray requisitions to limit patient radiation exposure as part of diagnostic imaging standard of care. DMARD treatment dose escalation and therapy changes will be measured to evaluate the primary objective. A sample size of

Rheumatoid Arthritis

MedlinePlus

... Education Visitor Information RePORT NIH Fact Sheets Home > Rheumatoid Arthritis Small Text Medium Text Large Text Rheumatoid Arthritis Rheumatoid arthritis is an inflammatory disease affecting about ...

Repeated exposure to antibiotics in infancy: a predisposing factor for juvenile idiopathic arthritis or a sign of this group's greater susceptibility to infections?

PubMed

Arvonen, Miika; Virta, Lauri J; Pokka, Tytti; Kröger, Liisa; Vähäsalo, Paula

2015-03-01

Previous exposure to antibiotics has been associated with the pathogenesis of several autoimmune diseases. Our objective was to explore whether childhood exposure to antibiotics would be associated with the risk of developing juvenile idiopathic arthritis (JIA). The material was collected from national registers containing all children born in 2000-2010 in Finland and diagnosed with JIA by the end of December 2012 (n = 1298) and appropriate controls (n = 5179) matched for age, sex, and place of birth. All purchases of antibiotics were collected from birth until the index date (i.e., the date of special reimbursement for JIA medications). A conditional logistic regression was performed to evaluate the association between the exposure to antibiotics and the risk of JIA. The risk of JIA increased with the number of antibiotic purchases from birth to the index date: for ≥ 1 purchases versus none, OR 1.6, 95% CI 1.3-1.9 with an upward trend in OR (p < 0.001). Antibiotic groups lincosamides and cephalosporins showed the strongest association with JIA (OR 6.6, 95% CI 3.7-11.7, and OR 1.6, 95% CI 1.4-1.8, respectively). Overall exposure to antibiotics before 2 years of age was associated with an increased risk of JIA (OR 1.4, 95% CI 1.2-1.6), with the trend test of OR (p < 0.001). Previous early and repeated exposure to antibiotics may predispose individuals to develop JIA. Alternatively, the apparent association may reflect shared susceptibility to infections and JIA.

Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial.

PubMed

Fleischmann, Roy; Mysler, Eduardo; Hall, Stephen; Kivitz, Alan J; Moots, Robert J; Luo, Zhen; DeMasi, Ryan; Soma, Koshika; Zhang, Richard; Takiya, Liza; Tatulych, Svitlana; Mojcik, Christopher; Krishnaswami, Sriram; Menon, Sujatha; Smolen, Josef S

2017-07-29

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. The Oral Rheumatoid Arthritis triaL (ORAL) Strategy aimed to assess the comparative efficacy of tofacitinib monotherapy, tofacitinib plus methotrexate, and adalimumab plus methotrexate for the treatment of rheumatoid arthritis in patients with a previous inadequate response to methotrexate. ORAL Strategy was a 1 year, double-blind, phase 3b/4, head-to-head, non-inferiority, randomised controlled trial in patients aged 18 years or older with active rheumatoid arthritis despite methotrexate therapy. Patients were randomly assigned (1:1:1) to receive oral tofacitinib (5 mg twice daily) monotherapy, oral tofacitinib (5 mg twice daily) plus methotrexate, or subcutaneous adalimumab (40 mg every other week) plus methotrexate at 194 centres in 25 countries. Eligible patients received live zoster vaccine at investigators' discretion. The primary endpoint was the proportion of patients who attained an American College of Rheumatology response of at least 50% (ACR50) at month 6 in the full analysis set (patients who were randomly assigned to a group and received at least one dose of the study treatment). Non-inferiority between groups was shown if the lower bound of the 98·34% CI of the difference between comparators was larger than -13·0%. This trial is registered with ClinicalTrials.gov, number NCT02187055. 1146 patients received treatment (384 had tofacitinib monotherapy; 376 had tofacitinib and methotrexate; and 386 had adalimumab and methotrexate). At 6 months, ACR50 response was attained in 147 (38%) of 384 patients with tofacitinib monotherapy, 173 (46%) of 376 patients with tofacitinib and methotrexate, and 169 (44%) of 386 patients with adalimumab and methotrexate. Non-inferiority was declared for tofacitinib and methotrexate versus adalimumab and methotrexate (difference 2% [98·34% CI -6 to 11]) but not for tofacitinib monotherapy versus either adalimumab and methotrexate (-6

Efficacy and Safety Outcomes for Originator TNF Inhibitors and Biosimilars in Rheumatoid Arthritis and Psoriasis Trials: A Systematic Literature Review.

PubMed

Moots, Robert J; Curiale, Cinzia; Petersel, Danielle; Rolland, Catherine; Jones, Heather; Mysler, Eduardo

2018-05-22

Regulatory approval of biosimilar versions of originator biotherapeutics requires that new biological products be highly similar to originator products, with no clinically meaningful differences in safety, purity, and potency. In some trials of biosimilars of tumor necrosis factor inhibitors for the treatment of rheumatoid arthritis (RA) and plaque psoriasis (PsO), pre-specified margins for efficacy and safety have been met, but differences in treatment responses between pivotal originator trials and biosimilar trials have been noted. The objective of this systematic review was to examine these differences. Searches were conducted to identify comparative randomized clinical trials of approved or proposed biosimilars of adalimumab, etanercept, and infliximab. Of 83 publications identified, 16 publications were included for analysis (RA: originators, n = 5; biosimilars, n = 6; PsO: originators, n = 2; biosimilars, n = 3). American College of Rheumatology 20% response rates were higher among patients with RA receiving originator biologics and biosimilars in biosimilar trials than among patients receiving the originator biologics in pivotal trials. In etanercept studies in PsO, a difference was observed in Psoriasis Area and Severity Index 75% response rates between biosimilar and pivotal trials. Insufficient efficacy data were available from adalimumab and infliximab biosimilar studies in PsO to determine any differences in treatment responses between pivotal and biosimilar studies. Observed differences in treatment response rates between pivotal originator trials and trials of originator biologics and their respective biosimilars may be attributable to fundamental differences in study design and/or baseline patient characteristics, which require further analysis.

Juvenile idiopathic arthritis patients and their skeletal status: possible role of vitamin D receptor gene polymorphism.

PubMed

Kostik, M M; Smirnov, A M; Demin, G S; Scheplyagina, L A; Larionova, V I

2014-01-01

We evaluated bone mineralization and metabolism changes related to vitamin D receptor (VDR) polymorphic genotypes in children with juvenile idiopathic arthritis. One hundred and ninety eight children (82 boys and 116 girls) were included in our study. Bone mineral density (BMD) was measured by lumbar spine DXA. Osteocalcin, CTX, parathyroid hormone, total and ionized calcium, inorganic phosphate, total alkaline phosphatase activity was utilized for assessment of bone metabolism. Molecular testing: TaqI (rs731236) and Cdx2 (rs11568820) polymorphisms of VDR were detected by RFLP. No differences in TaqI and Cdx2 haplotypes, genotypes and alleles distribution related with normal and low BMD (Zscore <-2SD) were found. Children with low linear growth (<10th percentile) had more allele T-contained genotypes of TagI VDR (p = 0.037), compare with medium or high linear growth children. Children with high linear growth (>90th percentile) had the highest frequency of allele A-contained genotypes (GA+AA) of Cdx2 VDR (p = 0.009). Girls with TT TaqI VDR, who never been treated by glucocorticoides had lower BMD-Zscore than C allele carriers (TT = -0.94SD [IQR: -2.1;-0.5], TC+CC = -0.62SD [IQR: -1.26;0.39], p = 0.03). Girls with Tanner I with TT had higher total and ionized Ca level than carriers of C allele (Ca: TT = 2.43 ± 0.15 mmol/l, TC+CC = 2.28 ± 0.2 mmol/l, p = 0.024; Ca(2+): TT = 1.15 ± 0.08 mmol/l, TC+CC = 1.06 ± 0.13 mmol/l, p = 0.026). Presence of TT genotype negatively correlated with BMD-Zscore (r = -0.28, p = 0.04), and positively with frequency of LBMD (r = 0.3, p = 0.037). Boy with GG Cdx2 genotype had lower total Ca (GG = 2.3 ± 0.17 mmol/l, GA+AA = 2.43 ± 0.17 mmol/l, p = 0.004) compare with carriers of A allele. Pubertal boys (Tanner IV-V) with GG had higher CTX (GG = 1.75 ± 0.11 ng/ml, GA+AA = 1.06 ± 0.07 ng/ml, p = 0.04. TT genotype of TaqI and GG genotype of Cdx2 VDR is a negative factor impact bone mineralization metabolism and linear growth.

Effect of periodontal treatment on the clinical parameters of patients with rheumatoid arthritis: study protocol of the randomized, controlled ESPERA trial

PubMed Central

2013-01-01

Background Rheumatoid arthritis (RA) is a chronic inflammatory disorder that leads to joint damage, deformity, and pain. It affects approximately 1% of adults in developed countries. Periodontitis is a chronic oral infection, caused by inflammatory reactions to gram-negative anaerobic bacteria, and affecting about 35 to 50% of adults. If left untreated, periodontitis can lead to tooth loss. A significant association has been shown to exist between periodontitis and RA in observational studies. Some intervention studies have suggested that periodontal treatment can reduce serum inflammatory biomarkers such as C-reactive protein, or erythrocyte sedimentation rate. We hypothesize that periodontitis could be an aggravating factor in patients with RA, and that its treatment would improve RA outcomes. The aim of this clinical trial is to assess the effect of periodontal treatment on the biological and clinical parameters of patients with RA. Methods/design The ESPERA (Experimental Study of Periodontitis and Rheumatoid Arthritis) study is an open-label, randomized, controlled trial. Subjects with both RA and periodontitis will be recruited at two university hospitals in southwestern France. In total, 40 subjects will be randomized into two arms (intervention and control groups), and will be followed up for 3 months. Intervention will consist of full-mouth supra-gingival and sub-gingival non-surgical scaling and root planing, followed by systemic antibiotic therapy, local antiseptics, and oral hygiene instructions. After the 3-month follow-up period, the same intervention will be applied to the subjects randomized to the control group. The primary outcome will be change of in Disease Activity Score in 28 Joints (DAS28) at the end of the follow-up period. Secondary outcomes will be the percentages of subjects with 20%, 50%, and 70% improvement in disease according to the American College of Rheumatology criteria. Health-related quality of life assessments (the Health

Methodological considerations for a randomised controlled trial of podiatry care in rheumatoid arthritis: lessons from an exploratory trial.

PubMed

Turner, Deborah E; Helliwell, Philip S; Woodburn, James

2007-11-06

Whilst evidence exists to support the use of single treatments such as orthoses and footwear, the effectiveness of podiatry-led care as a complex intervention for patients with rheumatoid arthritis (RA) related foot problems is unknown. The aim of this study was to undertake an exploratory randomised controlled parallel arm clinical trial (RheumAFooT) to inform the design and implementation of a definitive trial and to understand the potential benefits of this care. Patients with a definite diagnosis of RA, stable drug management 3 months prior to entry, and a current history of foot problems (pain, deformity, stiffness, skin or nail lesions, or footwear problems) were recruited from a hospital outpatient rheumatology clinic and randomised to receive 12 months of podiatry treatment or no care. The primary outcome was change in foot health status using the impairment/footwear (LFISIF) and activity limitation/participation restriction (LFISAP) subscales of the Leeds Foot Impact Scale. Disease Activity Score (DAS), Health Assessment Questionnaire (HAQ) score and walking speed (m/s) were also recorded. Of the 80 patients identified, 64 patients were eligible to participate in the pilot and 34 were recruited. 16 patients were randomised to receive podiatry led foot care and 18 received no care. Against a backdrop of stable disease (DAS and HAQ scores), there was a statistically significant between group difference in the change in foot health status for foot impairment (LFISIF) but not activity/participation (LFISAP) or function (walking speed) over 12 months. In the podiatry arm, 1 patient declined treatment following randomisation (did not want additional hospital visits) and 3 self-withdrew (lost to follow-up). Patients received an average of 3 consultations for assessment and treatment comprising routine care for skin and nail lesions (n = 3), foot orthoses (n = 9), footwear referral to the orthotist (n = 5), and ultrasound guided intra-articular steroid injection

Development of System-level Performance Measures for Evaluation of Models of Care for Inflammatory Arthritis in Canada.

PubMed

Barber, Claire E H; Marshall, Deborah A; Mosher, Dianne P; Akhavan, Pooneh; Tucker, Lori; Houghton, Kristin; Batthish, Michelle; Levy, Deborah M; Schmeling, Heinrike; Ellsworth, Janet; Tibollo, Heidi; Grant, Sean; Khodyakov, Dmitry; Lacaille, Diane

2016-03-01

To develop system-level performance measures for evaluating the care of patients with inflammatory arthritis (IA), including rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis, and juvenile idiopathic arthritis. This study involved several methodological phases. Over multiple rounds, various participants were asked to help define a set of candidate measurement themes. A systematic search was conducted of existing guidelines and measures. A set of 6 performance measures was defined and presented to 50 people, including patients with IA, rheumatologists, allied health professionals, and researchers using a 3-round, online, modified Delphi process. Participants rated the validity, feasibility, relevance, and likelihood of use of the measures. Measures with median ratings ≥ 7 for validity and relevance were included in the final set. Six performance measures were developed evaluating the following aspects of care, with each measure being applied separately for each type of IA except where specified: waiting times for rheumatology consultation for patients with new onset IA, percentage of patients with IA seen by a rheumatologist, percentage of patients with IA seen in yearly followup by a rheumatologist, percentage of patients with RA treated with a disease-modifying antirheumatic drug (DMARD), time to DMARD therapy in RA, and number of rheumatologists per capita. The first set of system-level performance measures for IA care in Canada has been developed with broad input. The measures focus on timely access to care and initiation of appropriate treatment for patients with IA, and are likely to be of interest to other arthritis care systems internationally.

Efficacy of Methylprednisolone Acetate Versus Triamcinolone Acetonide Intra-articular Knee Injection in Patients With Chronic Inflammatory Arthritis: A 24-Week Randomized Controlled Trial.

PubMed

Kumar, Ashwani; Dhir, Varun; Sharma, Shefali; Sharma, Aman; Singh, Surjit

2017-01-01

Triamcinolone hexacetonide (TH), triamcinolone acetonide (TA), and methylprednisolone acetate (MPA) are commonly used intra-articular steroid preparations. Studies suggest that intra-articular TH is more efficacious than MPA and TA in chronic inflammatory arthritis. However, it is unclear which of the latter two preparations has better efficacy. Thus, we compared intra-articular knee injections of MPA and TA in patients with chronic inflammatory arthritis. This double-blind, randomized controlled trial included patients with rheumatoid arthritis or spondyloarthritis with an acutely swollen knee joint (≥1 week, <24 weeks). They were randomly assigned (1:1) to intra-articular knee injection with MPA or TA (80 mg, 2 mL of each). Evaluations were performed at 4, 12, and 24 weeks. Primary outcome was time to relapse (Kaplan-Meier) over 24 weeks, with relapse defined as return to baseline pain or swelling ≥1 week. Secondary outcomes were change in pain and swelling (using a numerical rating scale), range of movement, and occurrence of adverse effects. Primary analysis was intention to treat, with last observation carried forward. One hundred patients (89 with rheumatoid arthritis) were randomly assigned in equal numbers to the MPA and TA groups. Nine patients relapsed in each group over 24 weeks. The mean time to relapse was not significantly different between the MPA and TA groups (20.8 [95% CI, 18.8-22.7] weeks and 20.9 [95% CI, 19.0-22.8] weeks, respectively; P = 0.9; hazard ratio = 1.0 [95% CI, 0.4-2.5]). In both groups, there was a significant decline in pain and swelling scores at all visits (P < 0.001); however, there were no significant intergroup differences. At 24 weeks, mean change in pain in the MPA (-4.4 [3.1]) and TA groups (-3.9 [2.8]) was not significantly different (P = 0.46). No infection, hematoma or hypopigmentation occurred in any patient. In addition, no significant intergroup differences were found in joint swelling, range of movement, modified

Evaluation of the association between Hispanic ethnicity and disease activity and severity in a large cohort of patients with juvenile idiopathic arthritis.

PubMed

Pelajo, Christina F; Angeles-Han, Sheila T; Prahalad, Sampath; Sgarlat, Caitlin M; Davis, Trevor E; Miller, Laurie C; Lopez-Benitez, Jorge M

2013-10-01

To examine the association between ethnicity and disease activity in patients with juvenile idiopathic arthritis (JIA), and to determine the association of ethnicity with disease severity and disability in this population. CARRAnet, a US database containing information (collected between May 2010 and June 2011) on almost 3,000 subjects with JIA, was used. Demographic variables were compared between Hispanic patients and non-Hispanic patients. Mann-Whitney and chi-square tests were used to compare indicators of disease activity, as well as imaging evidence of joint damage, and Childhood Health Assessment Questionnaire (CHAQ) scores between ethnicities. Two linear regression models were used to determine the association of ethnicity with number of active joints in JIA, and the association between ethnicity and disability (CHAQ scores). A total of 2,704 patients with JIA (277 Hispanic; 2,427 non-Hispanic) were included. Income and health insurance coverage were higher in non-Hispanics. RF-positive polyarticular JIA, positive RF and anti-CCP, as well as use of systemic steroids were more frequent in Hispanics. Imaging evidence of joint damage was present in 32 % of the Hispanic patients compared to 24 % of the non-Hispanic patients (p = 0.008). In multivariate linear regression analyses, the number of active joints was significantly higher in Hispanics than in non-Hispanics (p = 0.03), as well as CHAQ scores (p = 0.003), after adjusting for confounders. Hispanic patients with JIA had higher disease activity than non-Hispanic patients, as well as higher disease severity and disability. Since ethnicity influences disease activity, severity, and disability, different management and treatment plans should be planned accordingly.

Effectiveness of individual resource-oriented joint protection education in people with rheumatoid arthritis. A randomized controlled trial.

PubMed

Niedermann, Karin; de Bie, Rob A; Kubli, Regula; Ciurea, Adrian; Steurer-Stey, Claudia; Villiger, Peter M; Büchi, Stefan

2011-01-01

the modern joint protection (JP) concept for people with rheumatoid arthritis (RA) is an active coping strategy to improve daily tasks and role performance by changing working methods and using assistive devices. Effective group JP education includes psycho-educational interventions. The Pictorial Representation of Illness and Self Measure (PRISM) is an interactive hands-on-tool, assessing (a) the individual's perceived burden of illness and (b) relevant individual resources. Both issues are important for intrinsic motivation to take action and change behaviour. This study compared individual conventional JP education (C-JP) with PRISM-based JP education (PRISM-JP). an assessor-blinded multicentre randomized controlled trial, including four JP education sessions over 3 weeks, with assessments at baseline and 3 months. in total 53 RA patients participated. At 3 months, the PRISM-JP (n=26) participants did significantly better compared to the C-JP participants (n=27) in JP behaviour (p=0.02 and p=0.008 when corrected for baseline values), Arthritis Self-efficacy (ASES, p=0.015) and JP self-efficacy (JP-SES, p=0.047). Within-group analysis also showed less hand pain (p<0.001) in PRISM-JP group. PRISM-JP more effectively supported learning of JP methods, with meaningful occupations, resource activation and self-efficacy acting as important mediators. PRISM improved patient-clinician communication and is feasible for occupational therapy. 2010 Elsevier Ireland Ltd. All rights reserved.

HLA-DRB1*11 and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis.

PubMed

Ombrello, Michael J; Remmers, Elaine F; Tachmazidou, Ioanna; Grom, Alexei; Foell, Dirk; Haas, Johannes-Peter; Martini, Alberto; Gattorno, Marco; Özen, Seza; Prahalad, Sampath; Zeft, Andrew S; Bohnsack, John F; Mellins, Elizabeth D; Ilowite, Norman T; Russo, Ricardo; Len, Claudio; Hilario, Maria Odete E; Oliveira, Sheila; Yeung, Rae S M; Rosenberg, Alan; Wedderburn, Lucy R; Anton, Jordi; Schwarz, Tobias; Hinks, Anne; Bilginer, Yelda; Park, Jane; Cobb, Joanna; Satorius, Colleen L; Han, Buhm; Baskin, Elizabeth; Signa, Sara; Duerr, Richard H; Achkar, J P; Kamboh, M Ilyas; Kaufman, Kenneth M; Kottyan, Leah C; Pinto, Dalila; Scherer, Stephen W; Alarcón-Riquelme, Marta E; Docampo, Elisa; Estivill, Xavier; Gül, Ahmet; de Bakker, Paul I W; Raychaudhuri, Soumya; Langefeld, Carl D; Thompson, Susan; Zeggini, Eleftheria; Thomson, Wendy; Kastner, Daniel L; Woo, Patricia

2015-12-29

Systemic juvenile idiopathic arthritis (sJIA) is an often severe, potentially life-threatening childhood inflammatory disease, the pathophysiology of which is poorly understood. To determine whether genetic variation within the MHC locus on chromosome 6 influences sJIA susceptibility, we performed an association study of 982 children with sJIA and 8,010 healthy control subjects from nine countries. Using meta-analysis of directly observed and imputed SNP genotypes and imputed classic HLA types, we identified the MHC locus as a bona fide susceptibility locus with effects on sJIA risk that transcended geographically defined strata. The strongest sJIA-associated SNP, rs151043342 [P = 2.8 × 10(-17), odds ratio (OR) 2.6 (2.1, 3.3)], was part of a cluster of 482 sJIA-associated SNPs that spanned a 400-kb region and included the class II HLA region. Conditional analysis controlling for the effect of rs151043342 found that rs12722051 independently influenced sJIA risk [P = 1.0 × 10(-5), OR 0.7 (0.6, 0.8)]. Meta-analysis of imputed classic HLA-type associations in six study populations of Western European ancestry revealed that HLA-DRB1*11 and its defining amino acid residue, glutamate 58, were strongly associated with sJIA [P = 2.7 × 10(-16), OR 2.3 (1.9, 2.8)], as was the HLA-DRB1*11-HLA-DQA1*05-HLA-DQB1*03 haplotype [6.4 × 10(-17), OR 2.3 (1.9, 2.9)]. By examining the MHC locus in the largest collection of sJIA patients assembled to date, this study solidifies the relationship between the class II HLA region and sJIA, implicating adaptive immune molecules in the pathogenesis of sJIA.

Arthritis: Frequently Asked Questions

MedlinePlus

... Arthritis Types Osteoarthritis (OA) Rheumatoid Arthritis (RA) Fibromyalgia Gout Childhood Arthritis Managing Arthritis Risk Factors Physical Activity ... States is osteoarthritis. Other types of arthritis include gout, fibromyalgia, and rheumatoid arthritis. Learn about these common ...

Professional opinion concerning the effectiveness of bracing relative to observation in adolescent idiopathic scoliosis.

PubMed

Dolan, Lori A; Donnelly, Melanie J; Spratt, Kevin F; Weinstein, Stuart L

2007-01-01

To determine if community equipoise exists concerning the effectiveness of bracing in adolescent idiopathic scoliosis. Bracing is the standard of care for adolescent idiopathic scoliosis despite the lack of strong reasearch evidence concerning its effectiveness. Thus, some researchers support the idea of a randomized trial, whereas others think that randomization in the face of a standard of care would be unethical. A random of Scoliosis Research Society and Pediatric Orthopaedic Society of North America members were asked to consider 12 clinical profiles and to give their opinion concerning the radiographic outcomes after observation and bracing. An expert panel was created from the respondents. They expressed a wide array of opinions concerning the percentage of patients within each scenario who would benefit from bracing. Agreement was noted concerning the risk due to bracing for post-menarchal patients only. : This study found a high degree of variability in opinion among clinicians concerning the effectiveness of bracing, suggesting that a randomized trial of bracing would be ethical.

Rheumatoid Arthritis

MedlinePlus

Rheumatoid arthritis (RA) is a form of arthritis that causes pain, swelling, stiffness and loss of function in ... wrist and fingers. More women than men get rheumatoid arthritis. It often starts in middle age and is ...

Calcium pyrophosphate arthritis

MedlinePlus

... disease that can cause attacks of arthritis. Like gout, crystals form in the joints. But in this ... CPPD arthritis can be confused with: Gouty arthritis (gout) Osteoarthritis Rheumatoid arthritis Exams and Tests Most arthritic ...

Idiopathic Inflammatory Myopathies

PubMed Central

Dimachkie, Mazen M.; Barohn, Richard J.

2012-01-01

The idiopathic inflammatory myopathies are a group of rare disorders including polymyositis (PM), dermatomyositis (DM), and autoimmune necrotizing myopathies (NMs). The idiopathic inflammatory myopathies share many similarities. They present acutely, subacutely, or chronically with marked proximal and symmetric muscle weakness, except for associated distal and asymmetric weakness in inclusion body myositis. The idiopathic inflammatory myopathies also share a variable degree of creatine kinase (CK) elevation and a nonspecifically abnormal electromyogram demonstrating an irritative myopathy. The muscle pathology demonstrates inflammatory exudates of variable distribution within the muscle fascicle. Despite these similarities, the idiopathic inflammatory myopathies are a heterogeneous group. The overlap syndrome (OS) refers to the association of PM, DM, or NM with connective tissue disease, such as scleroderma or systemic lupus erythematosus. In addition to elevated antinuclear antibodies (ANA), patients with OS may be weaker in the proximal arms than the legs mimicking the pattern seen in some muscular dystrophies. In this review, we focus on DM, PM, and NM and examine current and promising therapies. PMID:23117947

Thermal imaging in screening of joint inflammation and rheumatoid arthritis in children.

PubMed

Lasanen, R; Piippo-Savolainen, E; Remes-Pakarinen, T; Kröger, L; Heikkilä, A; Julkunen, P; Karhu, J; Töyräs, J

2015-02-01

Potential of modern thermal imaging for screening and differentiation of joint inflammation has not been assessed in child and juvenile patient populations, typically demanding groups in diagnostics of musculoskeletal disorders. We hypothesize that thermal imaging can detect joint inflammation in patients with juvenile idiopathic arthritis or autoimmune disease with arthritis such as systemic lupus erythematosus. To evaluate the hypothesis, we studied 58 children exhibiting symptoms of joint inflammation. First, the patients' joints were examined along clinical procedure supplemented with ultrasound imaging when deemed necessary by the clinician. Second, thermal images were acquired from patients' knees and ankles. Results of thermal imaging were compared to clinical evaluations in knee and ankle. The temperatures were significantly (pmax = 0.044, pmean < 0.001) higher in inflamed ankle joints, but not in inflamed knee joints. No significant difference was found between the skin surface temperatures of medial and lateral aspects of ankle joints. In knee joints the mean temperatures of medial and lateral aspect differed significantly (p = 0.004). We have demonstrated that thermal imaging may have potential for detecting joint inflammation in ankle joints of children. For knee joints our results are inconclusive and further research is warranted.

Can Seeding in the Clinic Reach a Wide Audience? A Proof of Concept Study on Spreading a Health Message About Juvenile Idiopathic Arthritis Using a Shareable Online Video

PubMed Central

Fay, Michaela; Rapley, Tim; Foster, Helen; Pain, Clare

2016-01-01

Background Shareable online video offers the potential for spreading a health message across online and real world social networks. Seeding a message in a clinical setting may be advantageous. Objective To investigate the potential of an online video to spread a health message about juvenile idiopathic arthritis (JIA) when delivered or seeded in a clinical setting and investigate factors that influence sharing behavior. Methods Multimethod proof of concept study. Concepts for two different styles of video were developed using focus groups and interviews and reviewed by an online market research panel. We compared dissemination of the two videos from two specialist pediatric rheumatology clinics in NHS Hospitals. Participants were 15 patients, family members, and clinical staff with knowledge of JIA at concept stage; 300 market research panel members in development stage; and 38 patients and their parents or guardians in the seeding stage. Newly diagnosed patients with JIA and/or parents or guardians were invited to view and share an online video with a health message about JIA across real-life and electronic social networks. Main outcome measures were viewing statistics, sharing behavior and patterns, and participant feedback. Results Of 38 patients and/or their parents or guardians given links, 26 visited the video webpage and shared the link, 2 visited and did not share, and 10 did not visit. Most links were viewed and shared within a few days. A total of 3314 pageviews were recorded with a mean of 89.6 pageviews per link (range 0-1245). Links were accessed from 26 countries, with most viewers in the United Kingdom (82.5%). Mothers were the most active group of sharers. Conclusions Distribution of a video link in a clinical setting may be an effective way to spread a health message. Parents or guardians of children with JIA are more likely to share a link than young people. Dissemination depends on a small number of active sharers, the content of the video, and

Thumb Arthritis

MedlinePlus

Thumb arthritis Overview Thumb arthritis is common with aging, and occurs when cartilage wears away from the ends of the bones that form your thumb ... also known as the carpometacarpal (CMC) joint. Thumb arthritis can cause severe pain, swelling, and decreased strength ...

Preliminary definition of improvement in juvenile arthritis.

PubMed

Giannini, E H; Ruperto, N; Ravelli, A; Lovell, D J; Felson, D T; Martini, A

1997-07-01

To identify a core set of outcome variables for the assessment of children with juvenile arthritis (JA), to use the core set to develop a definition of improvement to determine whether individual patients demonstrate clinically important improvement, and to promote this definition as a single efficacy measure in JA clinical trials. A core set of outcome variables was established using a combination of statistical and consensus formation techniques. Variables in the core set consisted of 1) physician global assessment of disease activity; 2) parent/patient assessment of overall well-being; 3) functional ability; 4) number of joints with active arthritis; 5) number of joints with limited range of motion; and 6) erythrocyte sedimentation rate. To establish a definition of improvement using this core set, 21 pediatric rheumatologists from 14 countries met, and, using consensus formation techniques, scored each of 72 patient profiles as improved or not improved. Using the physicians' consensus as the gold standard, the chi-square, sensitivity, and specificity were calculated for each of 240 possible definitions of improvement. Definitions with sensitivity or specificity of <80% were eliminated. The ability of the remaining definitions to discriminate between the effects of active agent and those of placebo, using actual trial data, was then observed. Each definition was also ranked for face validity, and the sum of the ranks was then multiplied by the kappa statistic. The definition of improvement with the highest final score was as follows: at least 30% improvement from baseline in 3 of any 6 variables in the core set, with no more than 1 of the remaining variables worsening by >30%. The second highest scoring definition was closely related to the first; the third highest was similar to the Paulus criteria used in adult rheumatoid arthritis trials, except with different variables. This indicates convergent validity of the process used. We propose a definition of

Pirfenidone safety and adverse event management in idiopathic pulmonary fibrosis.

PubMed

Lancaster, Lisa H; de Andrade, Joao A; Zibrak, Joseph D; Padilla, Maria L; Albera, Carlo; Nathan, Steven D; Wijsenbeek, Marlies S; Stauffer, John L; Kirchgaessler, Klaus-Uwe; Costabel, Ulrich

2017-12-31

Pirfenidone is one of two approved therapies for the treatment of idiopathic pulmonary fibrosis (IPF). Randomised controlled clinical trials and subsequent post hoc analyses have demonstrated that pirfenidone reduces lung function decline, decreases mortality and improves progression-free survival. Long-term extension trials, registries and real-world studies have also shown similar treatment effects with pirfenidone. However, for patients with IPF to obtain the maximum benefits of pirfenidone treatment, the potential adverse events (AEs) associated with pirfenidone need to be managed. This review highlights the well-known and established safety profile of pirfenidone based on randomised controlled clinical trials and real-world data. Key strategies for preventing and managing the most common pirfenidone-related AEs are described, with the goal of maximising adherence to pirfenidone with minimal AEs. Copyright ©ERS 2017.

Clinical improvement of renal amyloidosis in a patient with systemic-onset juvenile idiopathic arthritis who received tocilizumab treatment: a case report and literature review.

PubMed

Chantarogh, Songkiat; Vilaiyuk, Soamarat; Tim-Aroon, Thipwimol; Worawichawong, Suchin

2017-05-12

Juvenile idiopathic arthritis (JIA) is a common rheumatic disease in children and adolescents. Although JIA may cause secondary amyloidosis, this is a rare complication in patients with JIA and other rheumatic diseases. Many previous studies have revealed that common heterozygous or homozygous mutations in the MEFV gene are associated with systemic-onset JIA (SJIA). We herein report a case involving a 19-year-old female patient with difficult-to-control SJIA. She developed progressive proteinuria without clinical signs or symptoms of edema. Renal amyloidosis was diagnosed by renal pathologic examination, which demonstrated deposition of eosinophilic amorphous material in the interlobular arteries, arterioles, and interstitium. Electron microscopy showed fibrillary material deposits with a diameter of 8 to 10 nm. A heterozygous E148Q mutation in the MEFV gene was identified. Conventional disease-modifying anti-rheumatic drugs and etanercept had been used to treat the SJIA, but the disease could not be controlled. Therefore, we decided to start tocilizumab to control the disease activity. However, the patient was unable to receive a standard dose of tocilizumab in the early period of treatment because of socioeconomic limitations. Her disease course was still active, and proteinuria was found. Therefore, tocilizumab was increased to a dose of 8 mg/kg every 2 weeks (standard dose of SJIA), and the patient exhibited a clinical response within 3 months. Refractory SJIA associated with renal amyloidosis is an uncommon cause of proteinuria in adolescents. Tocilizumab may be a beneficial treatment for renal amyloidosis in patients with SJIA.